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Showing VIPR1 — VPAC1 is a alias.

VIPR1

Vasoactive intestinal polypeptide receptor 1 · UniProt P32241

Length
457 aa
Mass
51.5 kDa
Annotated
2026-06-11
100 papers in source corpus 46 papers cited in narrative 45 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

VIPR1 (VPAC1) is a class B G protein-coupled receptor for the neuropeptides VIP and PACAP-27 that transduces these signals into cyclic AMP and calcium responses governing intestinal physiology, hematopoiesis, neural function, and inflammation (PMID:10801840, PMID:18000164). Ligand recognition follows a two-domain mechanism: the central-to-C-terminal portion of VIP (residues 6–22) docks against a negatively charged, tryptophan-lined groove in the N-terminal ectodomain, a Sushi/short-consensus-repeat fold stabilized by three disulfide bonds, while the VIP N-terminus engages the transmembrane bundle (PMID:11124960, PMID:16520374, PMID:15247290). Direct photoaffinity crosslinking mapped Phe6 to ectodomain residues 104–108 and Tyr22 to 109–120, and showed that the VIP His1 N-terminus contacts TM1 residues K143/T144/T147, contacts that are distinct from those used by antagonists (PMID:12807902, PMID:22291440). Receptor activation requires the acidic Asp3 of VIP to penetrate the transmembrane core and engage Arg188/Lys195 in TM2 within a conserved network linking Arg188 (TM2), Asn229 (TM3), and Gln380 (TM7) (PMID:11013258, PMID:20573782, PMID:16650965). Activated VPAC1 couples primarily to Gs/adenylyl cyclase via a DRY-equivalent 'YL' motif, and separately to Gi/Gq for calcium signaling through distinct third-intracellular-loop subdomains (IRKS 328–331 and distal basic residues R338/L339/R341) (PMID:15451021, PMID:11981043, PMID:11859928). Agonist-induced phosphorylation of C-terminal Ser/Thr residues drives desensitization (Ser447 as a GRK target) and internalization (PMID:15932876, PMID:14645688). Beyond canonical signaling, palmitoylation of Cys37 in the ectodomain directs VIP-induced nuclear translocation that supports anti-apoptotic activity, and a cleaved N-terminal signal peptide (residues 1–30) is required for surface expression (PMID:15518910, PMID:28473666). Physiologically, VPAC1 raises cAMP in megakaryocytes to suppress megakaryopoiesis and platelet production (PMID:18000164), is required for intestinal and pancreatic islet development (PMID:21697765), drives CFTR-dependent chloride secretion in epithelia by stabilizing CFTR through NHERF1/ERM (PMID:14744818, PMID:24788249), acts on cholinergic secretomotor and motor neurons to regulate intestinal secretion and motility (PMID:24578344), and mediates pro-inflammatory responses in colitis and EAE (PMID:21295288, PMID:27357191). Its transcription is suppressed by Ikaros and induced by FXR agonists in distinct epithelia (PMID:11812772, PMID:16037943).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2000 High

    Establishing which VIP residues drive VPAC1 engagement defined the pharmacophore and yielded the first selective VPAC1 agonist, enabling all subsequent receptor-subtype dissection.

    Evidence Alanine-scan VIP analogs with radioligand binding, adenylyl cyclase assays, and molecular modeling

    PMID:10801840

    Open questions at the time
    • Does not map the reciprocal receptor contact residues
    • Selectivity mechanism at the structural level not resolved
  2. 2001 High

    Identifying the transmembrane acidic-residue trigger answered how the VIP N-terminus converts binding into activation, separating activation from antagonist recognition.

    Evidence Site-directed mutagenesis of TM2 (Arg188, Lys195) with binding and cAMP assays in CHO cells

    PMID:11013258

    Open questions at the time
    • Conformational changes accompanying Asp3 insertion not directly observed
    • No structural snapshot of the activated state
  3. 2000 High

    Building a 3D model of the N-terminal ectodomain and validating its residues defined the peptide-binding groove architecture of the receptor.

    Evidence Homology modeling plus mutagenesis (Pro74, Pro87, Phe90, Trp110 etc.) with binding and cyclase readouts

    PMID:11124960

    Open questions at the time
    • Model lacks experimental high-resolution structure
    • Dynamics of ligand capture not addressed
  4. 2006 High

    Combining NMR of VIP with photoaffinity mapping resolved the two-domain binding mode, showing VIP 6–28 occupies the ectodomain while the N-terminus is free to reach the transmembrane region.

    Evidence Bpa photoaffinity probes at VIP positions 6/22/24, Edman sequencing, VIP NMR, and N-ted homology modeling/docking

    PMID:12807902 PMID:15247290 PMID:16520374

    Open questions at the time
    • Full receptor–ligand complex not crystallized
    • Stoichiometry and order of binding events not defined
  5. 2012 High

    Distinguishing agonist versus antagonist N-terminal contact sites and pinpointing TM1 His1-interacting residues clarified why agonists and antagonists are recognized differently.

    Evidence Bpa0 photoaffinity probes for VIP and PG97-269 plus alanine mutagenesis of TM1 (K143/T144/T147)

    PMID:18597186 PMID:22291440

    Open questions at the time
    • Functional consequence of distinct antagonist site for drug design not tested
    • Single-lab photoaffinity mapping
  6. 2010 High

    Demonstrating cooperativity among Arg188/Asn229/Gln380 established a conserved transmembrane activation network bridging ligand sensing and G-protein coupling.

    Evidence Structural modeling with double-mutant cooperativity analysis and cAMP/binding assays in CHO cells

    PMID:16650965 PMID:20573782

    Open questions at the time
    • Activation network not visualized structurally
    • Allosteric pathway to G protein not fully traced
  7. 2002 High

    Mapping intracellular-loop determinants showed VPAC1 uses physically separate subdomains for Gs/cAMP versus Gi/Gq/Ca2+ coupling, explaining its multifunctional signaling.

    Evidence VPAC1/VPAC2 chimeras and IC3 point mutants with aequorin calcium and cyclase assays; YL-motif mutagenesis

    PMID:11859928 PMID:11981043 PMID:15451021

    Open questions at the time
    • Direct G-protein selectivity at the structural interface not resolved
    • Cellular context dependence of coupling not addressed
  8. 2002 Medium

    Native pull-down showed tissue-dependent G-protein partners and basal pre-coupling, indicating VPAC1 coupling repertoire varies with cellular context.

    Evidence Immunoaffinity chromatography and cross-linking from human and rat tissues with G-protein-specific Western blots

    PMID:11812005

    Open questions at the time
    • Single-lab native study
    • Functional consequence of pre-coupling not established
  9. 2005 High

    Defining C-terminal Ser/Thr phosphorylation sites and Ser447 separated desensitization from internalization, clarifying receptor regulation kinetics.

    Evidence Truncation/site-directed mutagenesis with phosphorylation, internalization, recycling, flow cytometry, and confocal assays in CHO cells

    PMID:14645688 PMID:15932876

    Open questions at the time
    • GRK isoform identity not confirmed in vivo
    • Arrestin recruitment not directly measured
  10. 2004 High

    Establishing a cleavable N-terminal signal peptide explained the biogenesis requirement for surface delivery of VPAC1.

    Evidence Deletion and Flag-insertion constructs with binding, cAMP, and immunofluorescence localization in CHO cells

    PMID:15518910

    Open questions at the time
    • Cleavage site not directly sequenced
    • ER processing machinery not identified
  11. 2007 High

    Genetic and antibody studies established VPAC1 as a negative regulator of megakaryopoiesis acting through cAMP, defining a hematopoietic physiological role.

    Evidence CD34+ differentiation assays, neutralizing antibodies, transgenic and KO mice with cAMP and platelet readouts

    PMID:18000164

    Open questions at the time
    • Downstream cAMP effectors in megakaryocytes not detailed
    • Human therapeutic translation untested
  12. 2011 High

    VPAC1-null mice revealed an essential developmental role in intestine and endocrine pancreas, beyond acute signaling functions.

    Evidence Homozygous null mice and promoter-reporter localization with histology and glucose homeostasis assays

    PMID:21697765

    Open questions at the time
    • Cell-autonomous versus paracrine basis of phenotype unresolved
    • Molecular targets in islet development not identified
  13. 2014 High

    Identifying VPAC1 control of CFTR membrane stability via NHERF1/ERM and on cholinergic neurons defined dual epithelial and neural mechanisms for intestinal fluid secretion.

    Evidence Proximity ligation, siRNA knockdown, Ussing chamber, muscle contraction, and immunohistochemistry with selective pharmacology

    PMID:12598410 PMID:14744818 PMID:24578344 PMID:24788249

    Open questions at the time
    • Relative contribution of epithelial versus neuronal VPAC1 in vivo not quantified
    • Link between cAMP/PKC and scaffold remodeling not fully traced
  14. 2016 High

    KO and chimera studies in colitis and EAE established VPAC1 as a pro-inflammatory mediator, with CNS chemokine induction arising from non-hematopoietic VPAC1.

    Evidence VPAC1/VPAC2 KO mice, bone-marrow chimeras, adoptive transfer, cytokine/chemokine profiling, and pharmacological antagonists

    PMID:21295288 PMID:27357191

    Open questions at the time
    • Identity of non-hematopoietic VPAC1-expressing cells not pinned down
    • Mechanism of chemokine induction downstream of VPAC1 unresolved
  15. 2017 High

    Cys37 palmitoylation was shown to drive VIP-induced nuclear translocation linked to anti-apoptotic activity, revealing a non-canonical receptor function.

    Evidence C37A mutagenesis, acyl-biotin exchange and click-chemistry palmitoylation assays, 2-bromopalmitate, confocal imaging, and apoptosis assays in CHO cells

    PMID:28473666

    Open questions at the time
    • Nuclear targets of the translocated receptor unknown
    • In vivo relevance of nuclear VPAC1 untested
  16. 2022 Medium

    Cancer studies tied VPAC1 to metabolic and calcium-dependent signaling axes (ASS1/arginine and CAD in HCC; TRPV4/Ca2+ in gastric cancer), linking receptor activity to tumor growth control.

    Evidence In vitro/in vivo cancer cell studies with transcriptomics, calcium imaging, pathway analysis, and clinical sample correlation

    PMID:30692637 PMID:35864952

    Open questions at the time
    • Direct receptor-to-pathway coupling steps not fully reconstituted
    • Single-lab studies for each axis
  17. 2002 High

    Transcriptional control of VIPR1 was mapped to Ikaros-mediated suppression and, later, FXR-mediated induction, defining context-dependent expression regulation.

    Evidence EMSA/supershift, reporter deletions, and overexpression for Ikaros; FXR agonist with EMSA and expression assays in primary cells

    PMID:10331949 PMID:11812772 PMID:16037943

    Open questions at the time
    • Combinatorial control across tissues not integrated
    • Chromatin-level regulation incompletely defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of agonist-bound, G-protein-coupled VPAC1 and identification of the nuclear effectors of palmitoylation-dependent translocation remain open questions.
  • No experimental full-length receptor–ligand–G protein structure in the corpus
  • Nuclear signaling partners of translocated VPAC1 unidentified
  • Cell-type origin of pro-inflammatory VPAC1 effects unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0001618 virus receptor activity 1 GO:0048018 receptor ligand activity 1
Localization
GO:0005886 plasma membrane 2 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 3 R-HSA-1266738 Developmental Biology 2 R-HSA-382551 Transport of small molecules 2
Partners
ADCYAP1CFTRGNASNHERF1VIP

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Alanine scanning of VIP identified key residues (His1, Val5, Arg14, Lys15, Lys21, Leu23, Ile26) that directly interact with the VPAC1 receptor, and combining mutations at positions 11, 22, and 28 yielded the first highly selective (>1000-fold) VPAC1 agonist [Ala(11,22,28)]VIP. Solid-phase synthesis of VIP alanine-scan analogs, radioligand binding (125I-VIP), adenylyl cyclase activity assay, ab initio molecular modeling The Journal of biological chemistry High 10801840
2001 Two basic residues in the second transmembrane helix of VPAC1 (Arg188 and Lys195) are essential for receptor activation: the negatively charged Asp3 of VIP must penetrate into the transmembrane domain and interact with these residues to activate the receptor. This interaction is required for activation but not for antagonist recognition. Site-directed mutagenesis of VPAC1 receptor, radioligand binding, adenylyl cyclase activity assay in transfected CHO cells The Journal of biological chemistry High 11013258
2000 Three-dimensional model of the VPAC1 receptor N-terminal domain was constructed by homology modeling; site-directed mutagenesis confirmed that Pro74, Pro87, Phe90, and Trp110 (in addition to previously identified Glu36, Trp67, Asp68, Trp73, Gly109) are important for VIP binding and adenylyl cyclase activation, defining a negatively charged binding groove with a tryptophan shell. Homology modeling, site-directed mutagenesis, stable transfection in CHO cells, 125I-VIP binding, adenylyl cyclase activity assay The Journal of biological chemistry High 11124960
2003 Photoaffinity labeling with [Bpa22-VIP] demonstrated a direct physical contact between Tyr22 of VIP and the 109-120 fragment (GWTHLEPGPYPI) of the N-terminal ectodomain of hVPAC1 receptor, providing the first direct evidence for VIP–VPAC1 N-terminal ectodomain contact. Photoaffinity labeling, cyanogen bromide cleavage, V8 endoproteinase cleavage, creation of CNBr-cleavage-site receptor mutants, SDS-PAGE, Edman sequencing; 125I-labeled probe The Journal of biological chemistry High 12807902
2006 NMR structure of VIP (central alpha-helix, disordered N-terminal His1-Phe6, 310 helix at Ser25-Asn28) combined with photoaffinity labeling showed Phe6 contacts Asp107, Tyr22 contacts Gly116, and Asn24 contacts Cys122 in the N-terminal ectodomain of hVPAC1. A 3D model of the N-ted (short consensus repeat/Sushi domain with two antiparallel beta-sheets, three disulfide bonds) was built; docking showed the VIP 6-28 fragment occupies the C-terminal part of the N-ted while the N-terminus is free to interact with the transmembrane region. Photoaffinity labeling with Bpa at positions 6, 22, 24 of VIP, Edman sequencing of labeled fragments, NMR structure determination of VIP, homology modeling of N-ted using CRF receptor 2beta NMR structure as template, molecular docking The Journal of biological chemistry High 16520374
2004 Photoaffinity labeling with [Bpa6]-VIP demonstrated that position 6 of VIP contacts the 104-108 fragment of the hVPAC1 N-terminal ectodomain, adjacent to the fragment contacted by position 22 (Tyr22), showing that the central part of VIP (at least Phe6 to Tyr22) interacts with the N-terminal ectodomain. Photoaffinity labeling, sequential enzymatic and chemical cleavage (CNBr, PNGase F, Glu-C, trypsin), SDS-PAGE, receptor mutant with new CNBr cleavage site The Journal of biological chemistry High 15247290
2008 The N-terminal part of VIP (residues 1-5/0) physically contacts the 130-137 region of the hVPAC1 N-terminal ectodomain (via [Bpa0]-VIP probe), while the N-terminal part of antagonist PG97-269 contacts a different region of the N-ted (residues 43-66), demonstrating distinct binding sites for the agonist and antagonist N-termini. Photoaffinity labeling with Bpa0-VIP and Bpa0-PG97-269, CNBr cleavage, NuPAGE analysis Journal of molecular neuroscience Medium 18597186
2012 Photoaffinity labeling established that the N-terminus of VIP ([Bpa0]-VIP probe) contacts VPAC1 residue Q135, while the N-terminus of antagonist PG97-269 ([Bpa0]-PG97-269) contacts G62 of the N-ted—distinct from the VIP contact site. Additionally, residues K143, T144, and T147 in the first transmembrane domain are critical for interaction with the His1 N-terminus of VIP, as shown by alanine substitution. Photoaffinity labeling, alanine mutagenesis of transmembrane domain residues, binding affinity measurements, pharmacological assays with VIP2-28 FASEB journal High 22291440
2010 A network of conserved residues Arg188 (TM2), Asn229 (TM3), and Gln380 (TM7) governs ligand binding and receptor activation of VPAC1; double mutants of reciprocal residue exchanges showed strong cooperative or anticooperative effects confirming spatial proximity. Arg188 interacts with Asp3 of VIP and this is altered upon VIP binding to trigger activation. Structural modeling of TM domain, site-directed mutagenesis, cAMP production assay, binding assays, double mutant cooperativity analysis in CHO cells Molecular pharmacology High 20573782
2005 The carboxyl terminus of VPAC1 contains Ser/Thr residues (including Thr429, Ser435, Ser448/449, Ser455 in the distal C-terminus and Ser250 in the second intracellular loop) that mediate VIP-stimulated receptor phosphorylation and internalization; truncation removing all C-terminal Ser/Thr residues abolished phosphorylation and internalization, and also enabled receptor recycling (reversed within 2 h), an effect blocked by monensin. Site-directed mutagenesis and truncation of VPAC1, flow cytometry, confocal microscopy with monoclonal antibody against receptor, phosphorylation assays in CHO cells The Journal of biological chemistry High 15932876
2003 Ser447 in the C-terminal tail of VPAC1 is crucial for VIP-induced receptor phosphorylation and rapid desensitization (10-fold right-shift of ED50 for adenylyl cyclase) but is not required for receptor internalization or down-regulation; Ser447 is a likely GRK target. Site-directed mutagenesis to Ala, adenylyl cyclase activity assay, phosphorylation assay, internalization assay using fluorescein-tagged VIP and Flag/GFP-tagged receptor in CHO cells Molecular pharmacology High 14645688
2005 Mutations in the distal part of the third intracellular loop (R338, L339, R341) of VPAC1 markedly reduce VIP-stimulated calcium increase and Galphai coupling but only weakly affect adenylyl cyclase activity, whereas mutations in the proximal domain (K322) reduce adenylyl cyclase activity without changing the calcium response, demonstrating separate receptor sub-domains for Gs and Gi/Ca2+ coupling. Site-directed mutagenesis, adenylyl cyclase activity assay, calcium response assay in CHO cells Cellular signalling High 15451021
2002 A small sequence in the third intracellular loop (IC3) of VPAC1, residues 328-331 (IRKS), is responsible for efficient agonist-stimulated [Ca2+]i increase, likely through coupling to Galphai/Galphaq proteins; swapping this sequence with the VPAC2 counterpart (VGGN) interconverted the calcium signaling phenotypes of the two receptors. VPAC1/VPAC2 chimeric receptors, point mutations in IC3, aequorin reporter gene calcium assay in transfected CHO cells Molecular endocrinology High 11981043
1999 Specific mutations of Thr343 (to Lys, Pro, or Ala) in human VPAC1 receptor produced constitutive activation with ~3.5-fold increase in cAMP; constitutive activation required integrity of the N-terminal extracellular VIP-binding domain (abolished by E36A or D68A double mutations), establishing Thr343 at the IC2/TM4 junction as a key constraint for receptor activation state. Site-directed mutagenesis, transient transfection in COS cells, cAMP production assay, double-mutant analysis Biochemical and biophysical research communications High 9920725
2006 Asn229 in TM3 of VPAC1 is essential for receptor activation (G protein coupling) but not for VIP/antagonist binding, not for agonist-stimulated phosphorylation and internalization; the N229A mutant could still internalize but re-expressed more rapidly than wild-type after agonist washout, dissociating G protein activation from receptor trafficking. Site-directed mutagenesis (Ala, Asp, Gln mutations), adenylyl cyclase assay, calcium assay, GTP sensitivity assay, receptor phosphorylation and internalization assays in CHO cells Cellular signalling High 16650965
2001 The conserved 'YL' motif (Tyr239, Leu240) in VPAC1 is functionally equivalent to the 'DRY' motif of rhodopsin-family GPCRs; Y239A caused moderate and L240A caused pronounced impairment of VIP-induced cAMP production, primarily by perturbing the G protein-binding site rather than the intrinsic low-to-high affinity equilibrium. Site-directed mutagenesis, GTP-gamma-S binding shift assay, VIP-induced cAMP production in whole cells Journal of molecular neuroscience Medium 11859928
2001 Three conserved transmembrane prolines (P266, P300, P348) of VPAC1 are important for receptor expression, G protein coupling, and receptor activity; P266A decreased cAMP stimulation, while P300A and P348A increased potency and GTP sensitivity, suggesting these prolines constrain receptor activation. Adjacent leucines L346A and L349A also reduced receptor expression and G protein coupling. Alanine substitution mutagenesis, radioligand binding, cAMP production assay, GTP sensitivity in transfected cells FEBS letters Medium 11513868
2002 Immunoaffinity chromatography using an anti-VPAC1 first-extracellular-loop antibody showed that human VPAC1 in HEK293 cells couples to Gs but not Gi3, Gi1/2, or Gq; rat VPAC1 in brain couples to Gs and Gi3; rat VPAC1 in lung couples to Gs, Gi3, and Gq. VIP pretreatment increased G protein co-purification. Pre-coupling of VPAC1 to G protein occurred basally (without agonist), confirmed by covalent cross-linking. Immunoaffinity chromatography, covalent cross-linking in native membranes, Western blotting with G-protein-specific antibodies, 125I-VIP binding Biochemical and biophysical research communications Medium 11812005
2004 VPAC1 receptor contains a functional N-terminal signal peptide (residues 1-30); deletion of the signal peptide abolished cell-surface expression and 125I-VIP binding, while the signal peptide is cleaved during translocation to the plasma membrane, probably in the endoplasmic reticulum. Deletion and Flag-insertion constructs, stable transfection in CHO cells, 125I-VIP binding, cAMP production, GFP fluorescence, indirect immunofluorescence on non-permeabilized cells Regulatory peptides High 15518910
1999 VPAC1/VPAC2 chimeric receptor analysis showed the N-terminal extracellular domain determines selectivity for the VIP1 antagonist, while VPAC1-selective agonist recognition additionally requires the first extracellular loop and distal receptor domains; replacement of EC1 in VPAC1 with the VPAC2 counterpart markedly reduced maximal cAMP response. Chimeric VPAC1/VPAC2 receptors, radioligand binding, adenylyl cyclase activity assay European journal of biochemistry Medium 10491203
2004 VPAC1 receptor activation by VIP and PACAP-27 on the basolateral surface of human bronchial epithelial Calu-3 cells induces CFTR-dependent chloride secretion; this requires both PKA and PKC activity. IB3-1 cystic fibrosis cells expressing VPAC1 but lacking functional CFTR showed no chloride transport in response to VIP/PACAP-27. Radioligand binding (125I-VIP, 125I-PACAP-27), iodide efflux assay, Ussing chamber short-circuit current measurements, PKA inhibitor (H-89) and PKC inhibitor (chelerythrine) pharmacology British journal of pharmacology High 14744818
2014 VIP stimulation of VPAC1 in airway Calu-3 cells increases CFTR membrane stability by promoting CFTR interaction with NHERF1 and phosphorylated ERM (via PKCε), while reducing CFTR interaction with CFTR-associated ligand (CAL); knockdown of NHERF1 or ERM by siRNA prevented the VIP effect on CFTR membrane stability and sustained CFTR activity. Immunocytochemistry, in situ proximity ligation assay, siRNA knockdown of NHERF1 and ERM, iodide efflux assays, Western blotting American journal of physiology. Cell physiology High 24788249
2007 VPAC1 signaling negatively regulates megakaryopoiesis: PACAP/VIP activation of VPAC1 on megakaryocytes inhibits megakaryocyte differentiation and reduces platelet counts; blocking VPAC1 with neutralizing antibody (23A11) or anti-PACAP (PP1A4) inhibited cAMP formation, stimulated megakaryopoiesis independently of thrombopoietin, and elevated platelet counts in mice and in models of myelosuppression and GATA1 deficiency. In vitro CD34+ cell differentiation assays, anti-VPAC1 and anti-PACAP neutralizing antibodies, transgenic mice overexpressing PACAP in megakaryocytes, VPAC1 KO mouse studies, cAMP measurement, histology Blood High 18000164
2011 VPAC1 receptor mediates the pro-inflammatory enhancement of DSS-induced colitis by VIP: VPAC1-KO mice showed milder colitis than wild-type mice, with reduced tissue myeloperoxidase, IL-6, IL-1β, and MMP-9; suppression of VPAC1 signals by PKA inhibitors in VPAC2-KO mice reduced colitis severity. Thus VIP enhancement of colitis is exclusively mediated by VPAC1. VPAC1-KO and VPAC2-KO mice, DSS-induced colitis model, myeloperoxidase assay, cytokine measurement, histopathology, pharmacological PKA inhibitors Cellular immunology High 21295288
2016 VPAC1 deficiency ameliorates experimental autoimmune encephalomyelitis (EAE) by impairing the effector phase: VPAC1 KO mice showed reduced CNS histopathology, reduced chemokine mRNAs, and impaired inflammatory cell infiltration. WT cells fully induced EAE in WT but not VPAC1-KO recipients (bone marrow chimeras). The resistance was minimally dependent on VPAC1 expression in the hematopoietic compartment, implicating non-hematopoietic VPAC1 in CNS chemokine induction. VPAC1 KO mice, MOG35-55 EAE induction, histology, real-time PCR, immunofluorescence, adoptive transfer, bone marrow chimeras, antigen-recall assays, pharmacological VPAC1 antagonist Journal of neuroinflammation High 27357191
2011 VPAC1-null mice die perinatally with intestinal obstruction, disorganized hyperproliferative intestinal epithelium, small dysmorphic pancreatic islets, hypoglycemia, and impaired glucose homeostasis, demonstrating a required role for VPAC1 in embryonic and neonatal development of intestine and endocrine pancreas; VPAC1 promoter-driven transgene was expressed in E12.5/E14.5 intestinal epithelial and pancreatic endocrine cells. Homozygous VPAC1-null mutant mice, VPAC1 promoter-driven β-galactosidase transgenic mice, histology, glucose homeostasis assays (oral glucose tolerance, insulin challenge), blood glucose measurement Pancreas High 21697765
2002 VIP inhibits bone marrow progenitor proliferation (CFU-GM and erythroid progenitors) through VPAC1 (type 1 receptor), as shown by reversal of inhibition with VPAC1 antagonist but not VPAC2 agonist; direct effects on CD34+ cells were shown, with additional indirect effects via stromal TGF-β and TNF-α induction. Chemical cross-linking confirmed VPAC1 on stromal membranes. Clonogenic assays with unfractionated and CD34+ bone marrow cells, VPAC1/VPAC2 selective agonists and antagonists, semi-quantitative RT-PCR, chemical cross-linking Experimental hematology Medium 12225791
2014 VPAC1 receptor on cholinergic submucosal (NPY+) secretomotor neurons mediates VIP-induced chloride secretion: VIP-evoked secretion was depressed by VPAC1 antagonist PG97-269 and by hyoscine (muscarinic antagonist) but not eliminated by both together, indicating a direct epithelial VPAC1R component and an indirect VPAC1R-on-cholinergic-neuron component. VIP stimulates ACh-mediated longitudinal muscle contraction via VPAC1R on calretinin+ cholinergic motor neurons (inhibited by TTX, PG97-269, and hyoscine). Immunohistochemistry for VPAC1R and neurochemical markers, RT-PCR, Ussing chamber short-circuit current, isotonic muscle contraction with pharmacological dissection (TTX, VPAC1 antagonist PG97-269, hexamethonium, hyoscine) American journal of physiology. Gastrointestinal and liver physiology High 24578344
2009 VPAC1 receptor activation directs postnatal dentate gyrus neural stem/progenitor cells toward granule cell neurogenesis without a trophic effect, in contrast to VPAC2 which promotes symmetric division and nestin-positive cell pool expansion. This differential fate modulation was established by selective receptor agonists on postnatal hippocampal cultures. Selective VPAC1 and VPAC2 agonists applied to postnatal hippocampal cultures, cell fate analysis, BrdU incorporation, immunostaining for nestin and neuronal markers; in vivo Vipr2-/- mice for VPAC2 validation Stem cells Medium 19650041
2014 Microglial VPAC1R mediates VIP-induced enhancement of neural stem/progenitor cell proliferation and pro-neurogenic effects in hippocampal cultures via IL-4 release from microglia; conditioned media from VIP-stimulated microglia was trophic for NSPCs, and this was dependent on VPAC1 receptor signaling leading to IL-4 secretion. Hippocampal mixed cultures with microglial depletion and readdition, conditioned media experiments, VIP stimulation with VPAC1 receptor activation, IL-4 measurement, NSPC proliferation and survival assays Glia Medium 24801739
2005 VPAC1 receptor activation by VIP attenuates acute pancreatitis through inhibition of proinflammatory cytokine (IL-6, TNF-α) production from monocytes; selective VPAC1-R agonist decreased serum amylase, IL-6, and TNF-α and attenuated histological severity, while VPAC2-R agonist worsened outcomes. VPAC1-R and VPAC2-R mRNA were expressed in splenic monocytes. Cerulein/LPS mouse pancreatitis model, selective VPAC1-R and VPAC2-R agonists, serum amylase and cytokine ELISA, histology, in vitro monocyte cytokine production assay with LPS stimulation, RT-PCR Pancreas Medium 15632701
2003 VIP inhibits intestinal dipeptide (Gly-Sar) transport via VPAC1 receptor in Caco-2 cells (VPAC2 mRNA not expressed) by a PKA-dependent mechanism; the inhibition is Na+-dependent and involves reduction of NHE3-dependent intracellular pH recovery after dipeptide-induced acidification, indicating modulation of hPepT1 activity indirectly through NHE3 inhibition. 14C-Gly-Sar uptake assay, RT-PCR for receptor expression, BCECF pH measurement, PKA inhibitor H-89, NHE3 inhibitor S1611, Western blotting for NHERF1, selective VPAC1 agonist British journal of pharmacology Medium 12598410
2002 VPAC1 receptor actively facilitates productive HIV-1 infection: VPAC1 signal-blocking antibody inhibited ~80% of productive HIV-1 infection; VPAC1 antisense transfection reduced productive infection by ~50%; sense VPAC1 transfection increased productive infection >15-fold and increased syncytium formation. VPAC1 does not affect viral entry but is required for steps post-entry (absence of 2-LTR circles in VPAC1-negative cells). HIV-1 gp120 has sequence similarity to VIP, suggesting potential direct receptor activation. VPAC1 signal-blocking antibody, sense/antisense transfection of VPAC1 cDNA, HIV-1 p24 ELISA, luciferase pseudovirus assay, HIV-1 gag DNA PCR, 2-LTR circle analysis, syncytium formation assay AIDS Medium 11834941
2002 Ikaros transcription factors (IK-1 and IK-2) suppress endogenous VPAC1 expression: Ikaros binds high-affinity consensus sequences in the VPAC1 5'-flanking region (confirmed by EMSA with supershifts), overexpression of IK-1 or IK-2 in NIH-3T3 clones reduced VPAC1 mRNA and protein by 50-93%, and VPAC1 luciferase reporter activity was decreased up to 41% with two major Ikaros binding domains at -1076 to -623 bp and -222 to -35 bp. EMSA with native T cell nuclear extracts and recombinant IK-1/IK-2, antibody supershift, stable NIH-3T3 clones overexpressing Ikaros isoforms, RT-PCR and fluorometric kinetic RT-PCR, 125I-VIP binding, luciferase reporter with nested deletions The Journal of biological chemistry High 11812772
2005 VPAC1 receptor expression in gallbladder epithelial cells is transcriptionally regulated by FXR (farnesoid X receptor): the FXR agonist GW4064 upregulated VPAC1 mRNA and protein in primary human gallbladder epithelial cells dose-dependently; this effect was antagonized by 9-cis retinoic acid (RXRα ligand). Chenodeoxycholate activated endogenous FXR (confirmed by EMSA) and also increased VPAC1 expression. Quantitative RT-PCR, Western blot, primary human gallbladder epithelial cell cultures, pharmacological FXR agonist GW4064, EMSA for FXR binding, RXRα antagonism Hepatology Medium 16037943
2017 VPAC1 is localized to the apical membrane of intestinal epithelial cells (colocalizing with villin but not basolateral Na+/K+-ATPase) in both mouse and human colon, with highest expression in the colon compared to ileum and jejunum; this apical localization was determined by immunofluorescence and suggests potential for luminal peptide recognition. Quantitative RT-PCR, Western blotting, immunofluorescence with apical (villin) and basolateral (Na+/K+-ATPase) markers in mouse and human intestinal tissue American journal of physiology. Gastrointestinal and liver physiology Medium 28385693
2017 Palmitoylation of Cys37 in the N-terminal extracellular domain of VPAC1 mediates VIP-induced nuclear translocation of the receptor, which contributes to its anti-apoptotic activity; the C37A mutant failed to undergo nuclear translocation upon VIP stimulation and showed reduced anti-apoptotic activity, while exhibiting higher proliferative activity. Palmitoylation was confirmed by acyl-biotin exchange assay and click chemistry-based palmitoylation assay; the palmitoylation inhibitor 2-bromopalmitate blocked both nuclear translocation and anti-apoptotic activity. Site-directed mutagenesis (C37A), stable transfection with VPAC1-EYFP fusion proteins in CHO cells, confocal microscopy, Western blotting, fluorescence quantification, acyl-biotin exchange assay, click chemistry palmitoylation assay, 2-bromopalmitate treatment, apoptosis assay with camptothecin Oncotarget High 28473666
2019 VPAC1 activation by VIP in gastric cancer cells induces TRPV4-mediated Ca2+ entry and promotes gastric cancer progression in a Ca2+-dependent manner; this VPAC1/TRPV4/Ca2+ signaling axis enhances VIP expression and secretion, establishing a positive autocrine feedback loop. Inhibition of VPAC1 blocked progressive responses. In vitro gastric cancer cell signaling assays, Ca2+ imaging, VPAC1 and TRPV4 inhibition, VIP/VPAC1 expression analysis in human cancer specimens and cell lines Oncogene Medium 30692637
2022 VIPR1 activation by VIP in HCC cells inhibits growth and metastasis through regulation of arginine biosynthesis: VIP treatment partially restored argininosuccinate synthase (ASS1) expression and inhibited de novo pyrimidine synthesis by suppressing CAD phosphorylation via mTOR/p70S6K signaling. Human HCC samples showed downregulation of ASS1 and upregulation of phospho-CAD correlating with VIPR1 loss. In vitro and in vivo HCC cell studies with VIP treatment, transcriptome sequencing, ASS1 expression analysis, CAD phosphorylation assay, mTOR/p70S6K pathway analysis, human HCC clinical sample analysis International journal of biological sciences Medium 35864952
2005 VPAC1 and VPAC2 receptors are both required for pressure-induced vasodilatation (PIV): blockade of VPAC1/VPAC2, or selectively of VPAC1 alone, eliminated the PIV response in anesthetized rodents, while PAC1 blockade had no effect. Vascular smooth muscle and endothelial vasodilator capacity were unaffected by VPAC1/2 antagonism. In vivo pharmacological blockade with selective antagonists (PG97-269 for VPAC1, PACAP6-38 for VPAC2/PAC1, Max.d.4 for PAC1, D-p-Cl-Phe6,Leu17-VIP for VPAC1/2) in anesthetized rodents, laser Doppler flowmetry The Journal of physiology Medium 14578481
2006 In porcine basilar arteries, VPAC1 receptor is localized specifically on the endothelium and mediates vasodilation via nitric oxide (NO) generation (inhibited by L-NAME, abolished by endothelial denudation), while VPAC2 on outer smooth muscle layers mediates NO-independent vasodilation. Immunocytochemistry, RT-PCR, pharmacological vasodilator responses to selective receptor agonists, L-NAME inhibition, endothelial denudation, electrical stimulation with VPAC2 antagonist Journal of cerebral blood flow and metabolism Medium 15959462
2011 VPAC1 receptor on hippocampal nerve terminals inhibits exocytotic VGCC-dependent GABA release through Gi/o protein- and PKC-dependent mechanisms; this opposes the VPAC2 receptor effect (which enhances GABA release via Gs/PKA/PKC). Isolated rat hippocampal nerve terminal preparations, 3H-GABA release assay with selective VPAC1/VPAC2 agonists and antagonists, pertussis toxin, PKA inhibitor, PKC inhibitor, voltage-gated calcium channel blockers British journal of pharmacology Medium 28945273
2005 VPAC1 receptor activation by VIP and PACAP enhances hippocampal CA1 pyramidal cell synaptic transmission; VPAC1-mediated enhancement is dependent on PKC but not PKA activity (in contrast to VPAC2-mediated enhancement which requires PKA), demonstrating distinct intracellular signaling downstream of each receptor subtype in hippocampal synaptic modulation. Selective VPAC1 agonist [K15,R16,L27]VIP(1-7)/GRF(8-27) and VPAC2 agonist RO 25-1553, selective antagonists PG97-269 and PG99-465, PKA inhibitor H-89, PKC inhibitor GF109203X, field potential recording in hippocampal slices Brain research Medium 15935995
2008 In CD4 T cells, VPAC1 mRNA is upregulated by the vascular environment but downregulated by TCR signaling (anti-CD3); JNK kinases downstream of Zap70 mediate the suppressive regulation of VPAC1 after TCR activation, while inhibitors of PKC, ERK, p38, Zap70, and Rac1 show stimulatory influence on VPAC1 expression in the absence of TCR signaling. Primary murine splenic CD4 T cell isolation, pharmacological kinase inhibitors (10 inhibitors), anti-CD3 stimulation, qPCR for VPAC1 mRNA, blood vs. spleen comparison Brain, behavior, and immunity Medium 18534815 18555660
1999 The mouse Vipr1 gene is encoded on chromosome 9 (syntenic with human chromosome 3p21.3) in a single-copy gene of >16 kb with 13 exons; the 5'-flanking region lacks a TATA box but contains a CCAAT box, Sp1- and AP-2-binding sites, and has functional promoter activity in luciferase reporter assays. Genomic cloning and sequencing, exon-intron mapping, chromosomal mapping by genetic crosses, luciferase reporter assay Genomics Medium 10331949

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 The endogenous lipid anandamide is a full agonist at the human vanilloid receptor (hVR1). British journal of pharmacology 631 10694225
2004 Distribution of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide receptors (VPAC1, VPAC2, and PAC1 receptor) in the rat brain. The Journal of comparative neurology 162 15282712
2000 Identification of key residues for interaction of vasoactive intestinal peptide with human VPAC1 and VPAC2 receptors and development of a highly selective VPAC1 receptor agonist. Alanine scanning and molecular modeling of the peptide. The Journal of biological chemistry 141 10801840
1998 Genetic complexity of the hypervariable region 1 (HVR1) of hepatitis C virus (HCV): influence on the characteristics of the infection and responses to interferon alfa therapy in patients with chronic hepatitis C. Journal of medical virology 98 9557291
1996 Differential expression of vasoactive intestinal peptide receptors 1 and 2 (VIP-R1 and VIP-R2) mRNA in murine lymphocytes. Journal of neuroimmunology 98 8784257
2004 Immunocytochemical identification of VPAC1, VPAC2, and PAC1 receptors in normal and neoplastic human tissues with subtype-specific antibodies. Clinical cancer research : an official journal of the American Association for Cancer Research 89 15623599
2000 Immunohistochemical localization of the VIP1 receptor (VPAC1R) in rat cerebral blood vessels: relation to PACAP and VIP containing nerves. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 78 10950381
2001 Two basic residues of the h-VPAC1 receptor second transmembrane helix are essential for ligand binding and signal transduction. The Journal of biological chemistry 77 11013258
2012 Spontaneous clearance of primary acute hepatitis C virus infection correlated with high initial viral RNA level and rapid HVR1 evolution. Hepatology (Baltimore, Md.) 58 22234804
2006 Peptide agonist docking in the N-terminal ectodomain of a class II G protein-coupled receptor, the VPAC1 receptor. Photoaffinity, NMR, and molecular modeling. The Journal of biological chemistry 58 16520374
2015 Monoclonal Antibodies Directed toward the Hepatitis C Virus Glycoprotein E2 Detect Antigenic Differences Modulated by the N-Terminal Hypervariable Region 1 (HVR1), HVR2, and Intergenotypic Variable Region. Journal of virology 47 26378182
2010 Replacing adenoviral vector HVR1 with a malaria B cell epitope improves immunogenicity and circumvents preexisting immunity to adenovirus in mice. The Journal of clinical investigation 47 20811151
2007 PET imaging of VPAC1 expression in experimental and spontaneous prostate cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 45 18077536
1996 Murine T-lymphocytes express vasoactive intestinal peptide receptor 1 (VIP-R1) mRNA. Journal of neuroimmunology 45 8784267
2012 Three different functional microdomains in the hepatitis C virus hypervariable region 1 (HVR1) mediate entry and immune evasion. The Journal of biological chemistry 42 22927442
2004 Activation of VPAC1 receptors by VIP and PACAP-27 in human bronchial epithelial cells induces CFTR-dependent chloride secretion. British journal of pharmacology 42 14744818
2003 Photoaffinity labeling demonstrates physical contact between vasoactive intestinal peptide and the N-terminal ectodomain of the human VPAC1 receptor. The Journal of biological chemistry 41 12807902
2015 HVR1-mediated antibody evasion of highly infectious in vivo adapted HCV in humanised mice. Gut 40 26589670
2019 VPAC1 couples with TRPV4 channel to promote calcium-dependent gastric cancer progression via a novel autocrine mechanism. Oncogene 39 30692637
2018 Role of the E2 Hypervariable Region (HVR1) in the Immunogenicity of a Recombinant Hepatitis C Virus Vaccine. Journal of virology 39 29540595
2010 Design and in vitro characterization of PAC1/VPAC1-selective agonists with potent neuroprotective effects. Biochemical pharmacology 39 21114961
2005 Characterization of four receptor cDNAs: PAC1, VPAC1, a novel PAC1 and a partial GHRH in zebrafish. Molecular and cellular endocrinology 39 15713535
2002 Elucidation of vasoactive intestinal peptide pharmacophore for VPAC(1) receptors in human, rat, and guinea pig. The Journal of pharmacology and experimental therapeutics 39 11907155
1999 A cloned frog vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating polypeptide receptor exhibits pharmacological and tissue distribution characteristics of both VPAC1 and VPAC2 receptors in mammals. Endocrinology 39 10067855
2007 PACAP and its receptor VPAC1 regulate megakaryocyte maturation: therapeutic implications. Blood 38 18000164
2003 Evidence for the involvement of VPAC1 and VPAC2 receptors in pressure-induced vasodilatation in rodents. The Journal of physiology 38 14578481
2005 VIP attenuation of the severity of experimental pancreatitis is due to VPAC1 receptor-mediated inhibition of cytokine production. Pancreas 37 15632701
2000 The human VPAC1 receptor: three-dimensional model and mutagenesis of the N-terminal domain. The Journal of biological chemistry 37 11124960
2009 The neurotransmitter VIP expands the pool of symmetrically dividing postnatal dentate gyrus precursors via VPAC2 receptors or directs them toward a neuronal fate via VPAC1 receptors. Stem cells (Dayton, Ohio) 36 19650041
2005 Genetic history of some western Mediterranean human isolates through mtDNA HVR1 polymorphisms. Journal of human genetics 36 16307178
2014 Microglial VPAC1R mediates a novel mechanism of neuroimmune-modulation of hippocampal precursor cells via IL-4 release. Glia 35 24801739
2006 Location and function of VPAC1, VPAC2 and NPR-C receptors in VIP-induced vasodilation of porcine basilar arteries. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 35 15959462
2017 Expression and localization of VPAC1, the major receptor of vasoactive intestinal peptide along the length of the intestine. American journal of physiology. Gastrointestinal and liver physiology 34 28385693
2011 Characterization of intestinal and pancreatic dysfunction in VPAC1-null mutant mouse. Pancreas 34 21697765
2005 VPAC1 expression is regulated by FXR agonists in the human gallbladder epithelium. Hepatology (Baltimore, Md.) 34 16037943
2011 VPAC1 (vasoactive intestinal peptide (VIP) receptor type 1) G protein-coupled receptor mediation of VIP enhancement of murine experimental colitis. Cellular immunology 32 21295288
2005 Contribution of the carboxyl terminus of the VPAC1 receptor to agonist-induced receptor phosphorylation, internalization, and recycling. The Journal of biological chemistry 32 15932876
2002 Vasoactive intestinal peptide (VIP) inhibits the proliferation of bone marrow progenitors through the VPAC1 receptor. Experimental hematology 32 12225791
2000 Molecular epidemiology of an outbreak of HCV in a hemodialysis unit: direct sequencing of HCV-HVR1 as an appropriate tool for phylogenetic analysis. Journal of medical virology 31 10596014
2018 Upregulation of intestinal mucosal mast cells expressing VPAC1 in close proximity to vasoactive intestinal polypeptide in inflammatory bowel disease and murine colitis. Neurogastroenterology and motility 30 30407703
2014 VPAC1 receptors regulate intestinal secretion and muscle contractility by activating cholinergic neurons in guinea pig jejunum. American journal of physiology. Gastrointestinal and liver physiology 30 24578344
2002 Elucidation of the vasoactive intestinal peptide pharmacophore for VPAC(2) receptors in human and rat and comparison to the pharmacophore for VPAC(1) receptors. The Journal of pharmacology and experimental therapeutics 29 12388623
2004 Diffuse pharmacophoric domains of vasoactive intestinal peptide (VIP) and further insights into the interaction of VIP with the N-terminal ectodomain of human VPAC1 receptor by photoaffinity labeling with [Bpa6]-VIP. The Journal of biological chemistry 28 15247290
2010 Evidence that interaction between conserved residues in transmembrane helices 2, 3, and 7 are crucial for human VPAC1 receptor activation. Molecular pharmacology 27 20573782
2000 VPAC1 receptors and lung cancer. Annals of the New York Academy of Sciences 27 11193832
2013 VPAC1 receptors for imaging breast cancer: a feasibility study. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 26 23651947
2011 RNA interference-directed silencing of VPAC1 receptor inhibits VIP effects on both EGFR and HER2 transactivation and VEGF secretion in human breast cancer cells. Molecular and cellular endocrinology 26 21896307
2005 VIP enhances synaptic transmission to hippocampal CA1 pyramidal cells through activation of both VPAC1 and VPAC2 receptors. Brain research 26 15935995
2022 Activation of VIPR1 suppresses hepatocellular carcinoma progression by regulating arginine and pyrimidine metabolism. International journal of biological sciences 25 35864952
2016 VPAC1 receptor (Vipr1)-deficient mice exhibit ameliorated experimental autoimmune encephalomyelitis, with specific deficits in the effector stage. Journal of neuroinflammation 25 27357191
2010 Anti-hyperglycemic, antioxidant and anti-inflammatory effects of VIP and a VPAC1 agonist on streptozotocin-induced diabetic mice. Peptides 25 21129425
1996 Comparison of hypervariable regions (HVR1 and HVR2) in positive- and negative-stranded hepatitis C virus RNA in cancerous and non-cancerous liver tissue, peripheral blood mononuclear cells and serum from a patient with hepatocellular carcinoma. International journal of cancer 25 8760588
2015 VPAC1 Targeted (64)Cu-TP3805 Positron Emission Tomography Imaging of Prostate Cancer: Preliminary Evaluation in Man. Urology 24 26519886
2014 VPAC1 overexpression is associated with poor differentiation in colon cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 24 24671823
2005 Mutations in the carboxy-terminus of the third intracellular loop of the human recombinant VPAC1 receptor impair VIP-stimulated [Ca2+]i increase but not adenylate cyclase stimulation. Cellular signalling 24 15451021
2004 Presence of a N-terminal signal peptide in class II G protein-coupled receptors: crucial role for expression of the human VPAC1 receptor. Regulatory peptides 23 15518910
2003 Inhibition of intestinal dipeptide transport by the neuropeptide VIP is an anti-absorptive effect via the VPAC1 receptor in a human enterocyte-like cell line (Caco-2). British journal of pharmacology 23 12598410
1999 Vasoactive intestinal polypeptide VPAC1 and VPAC2 receptor chimeras identify domains responsible for the specificity of ligand binding and activation. European journal of biochemistry 23 10491203
2019 Mechanism of VIPR1 gene regulating human lung adenocarcinoma H1299 cells. Medical oncology (Northwood, London, England) 22 31560089
2017 VPAC1 and VPAC2 receptor activation on GABA release from hippocampal nerve terminals involve several different signalling pathways. British journal of pharmacology 22 28945273
2004 Duplicated receptors for VIP and PACAP (VPAC1R and PAC1R) in a teleost fish, Fugu rubripes. Journal of molecular endocrinology 22 15525598
2003 Serine 447 in the carboxyl tail of human VPAC1 receptor is crucial for agonist-induced desensitization but not internalization of the receptor. Molecular pharmacology 22 14645688
2002 VPAC1 is a cellular neuroendocrine receptor expressed on T cells that actively facilitates productive HIV-1 infection. AIDS (London, England) 22 11834941
2017 The palmitoylation of the N-terminal extracellular Cys37 mediates the nuclear translocation of VPAC1 contributing to its anti-apoptotic activity. Oncotarget 21 28473666
2012 Spatial proximity between the VPAC1 receptor and the amino terminus of agonist and antagonist peptides reveals distinct sites of interaction. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 22291440
2002 Vasoactive intestinal peptide receptor-1 (VPAC-1) is a novel gene target of the hemolymphopoietic transcription factor Ikaros. The Journal of biological chemistry 21 11812772
1999 Genomic organization and chromosomal location of the mouse vasoactive intestinal polypeptide 1 (VPAC1) receptor. Genomics 21 10331949
2014 VIP regulates CFTR membrane expression and function in Calu-3 cells by increasing its interaction with NHERF1 and P-ERM in a VPAC1- and PKCε-dependent manner. American journal of physiology. Cell physiology 20 24788249
2014 Endogenous inhibition of hippocampal LTD and depotentiation by vasoactive intestinal peptide VPAC1 receptors. Hippocampus 19 24935659
2010 Role of VPAC1 and VPAC2 in VIP mediated inhibition of rat pulmonary artery and aortic smooth muscle cell proliferation. Peptides 17 20452385
2009 VPAC1 receptor binding site: contribution of photoaffinity labeling approach. Neuropeptides 17 20031208
2002 A small sequence in the third intracellular loop of the VPAC(1) receptor is responsible for its efficient coupling to the calcium effector. Molecular endocrinology (Baltimore, Md.) 17 11981043
2000 Cross-chimeric analysis of selectivity of secretin and VPAC(1) receptor activation. The Journal of pharmacology and experimental therapeutics 17 11046106
2012 The VPAC1 receptor: structure and function of a class B GPCR prototype. Frontiers in endocrinology 16 23162538
2006 Asn229 in the third helix of VPAC1 receptor is essential for receptor activation but not for receptor phosphorylation and internalization: comparison with Asn216 in VPAC2 receptor. Cellular signalling 16 16650965
2006 Breast cancer VPAC1 receptors. Annals of the New York Academy of Sciences 16 16888206
2003 A lymphocyte-generated fragment of vasoactive intestinal peptide with VPAC1 agonist activity and VPAC2 antagonist effects. The Journal of pharmacology and experimental therapeutics 16 12750439
2008 Pituitary adenylate cyclase-activating polypeptide regulates brain-derived neurotrophic factor exon IV expression through the VPAC1 receptor in the amphibian melanotrope cell. Endocrinology 15 18450956
2008 The N-terminal parts of VIP and antagonist PG97-269 physically interact with different regions of the human VPAC1 receptor. Journal of molecular neuroscience : MN 15 18597186
2006 Vasoactive intestinal polypeptide (VIP) and VPAC1 receptor in adult human dental pulp in relation to caries. Archives of oral biology 15 16806045
2000 Creation of a selective antagonist and agonist of the rat VPAC(1) receptor using a combinatorial approach with vasoactive intestinal peptide 6-23 as template. Molecular pharmacology 15 11040051
1999 The human vasoactive intestinal Peptide/Pituitary adenylate cyclase activating peptide receptor 1 (VPAC1): constitutive activation by mutations at threonine 343. Biochemical and biophysical research communications 15 9920725
2018 Promoter methylation and H3K27 deacetylation regulate the transcription of VIPR1 in hepatocellular carcinoma. Biochemical and biophysical research communications 14 30583864
2004 Preferential expression of the vasoactive intestinal peptide (VIP) receptor VPAC1 in human cord blood-derived CD34+CD38- cells: possible role of VIP as a growth-promoting factor for hematopoietic stem/progenitor cells. Leukemia 14 14999295
2002 Identification of G-proteins coupling to the vasoactive intestinal peptide receptor VPAC(1) using immunoaffinity chromatography: evidence for precoupling. Biochemical and biophysical research communications 14 11812005
2001 Functional roles of conserved transmembrane prolines in the human VPAC(1) receptor. FEBS letters 14 11513868
2001 Characterization of a G protein coupling "YL" motif of the human VPAC1 receptor, equivalent to the first two amino acids in the "DRY" motif of the rhodopsin family. Journal of molecular neuroscience : MN 14 11859928
1999 Functional expression of rat VPAC1 receptor in Saccharomyces cerevisiae. Receptors & channels 14 10412720
2016 Clinical Relevance of VPAC1 Receptor Expression in Early Arthritis: Association with IL-6 and Disease Activity. PloS one 13 26881970
2013 Screening of a specific peptide binding to VPAC1 receptor from a phage display peptide library. PloS one 13 23365656
2008 TCR signaling and environment affect vasoactive intestinal peptide receptor-1 (VPAC-1) expression in primary mouse CD4 T cells. Brain, behavior, and immunity 13 18534815
2008 Stimulatory and suppressive signal transduction regulates vasoactive intestinal peptide receptor-1 (VPAC-1) in primary mouse CD4 T cells. Brain, behavior, and immunity 13 18555660
2000 Retinoic acid down-regulates VPAC(1) receptors and TGF-beta 3 but up-regulates TGF-beta 2 in lung cancer cells. Peptides 13 11150643
2022 The VIP/VPAC1R Pathway Regulates Energy and Glucose Homeostasis by Modulating GLP-1, Glucagon, Leptin and PYY Levels in Mice. Biology 12 35336804
2005 Reduced immunoreactivities of a vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide receptor (VPAC1 receptor) in the cerebral cortex, hippocampal region, and amygdala of aged rats. Brain research 12 16269138
2000 VIP activates G(s) and G(i3) in rat alveolar macrophages and G(s) in HEK293 cells transfected with the human VPAC(1) receptor. Biochemical and biophysical research communications 12 10860852
2022 Identification of the Diagnostic Biomarker VIPR1 in Hepatocellular Carcinoma Based on Machine Learning Algorithm. Journal of oncology 11 36157238
2022 PAC1, VPAC1, and VPAC2 Receptor Expression in Rat and Human Trigeminal Ganglia: Characterization of PACAP-Responsive Receptor Antibodies. International journal of molecular sciences 11 36430275
2010 Thrombopoietic effect of VPAC1 inhibition during megakaryopoiesis. British journal of haematology 11 20735399
2007 The neuropeptide pituitary adenylate cyclase activating polypeptide modulates Ca2+ and pro-inflammatory functions in human monocytes through the G protein-coupled receptors VPAC-1 and formyl peptide receptor-like 1. Cell calcium 11 17651798

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