Affinage

VIPR2

Vasoactive intestinal polypeptide receptor 2 · UniProt P41587

Length
438 aa
Mass
49.5 kDa
Annotated
2026-06-11
100 papers in source corpus 45 papers cited in narrative 45 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

VIPR2 (VPAC2) is a Gs-coupled class B receptor for the neuropeptides VIP and PACAP that, through cAMP/PKA signaling, governs intercellular coupling of the suprachiasmatic nucleus (SCN) circadian pacemaker and a broad set of neural, immune, and metabolic processes (PMID:12086606, PMID:16641377). In the SCN it is essential for sustained behavioral and molecular clock rhythms: Vipr2-null mice fail to maintain rest/activity rhythms, lose circadian clock-gene expression, lose the bulk of VIP-evoked SCN electrophysiological responses, and exhibit desynchronized, low-amplitude single-cell oscillations (PMID:12086606, PMID:12542655, PMID:18554318), while gain of VPAC2 expression shortens period and accelerates re-entrainment (PMID:11027354). VPAC2-expressing cells form a functionally powerful pacemaker subset whose intrinsic clock and circadian competence set ensemble period and phase (PMID:32636383, PMID:33234609), and VPAC2 signaling also gates photic input to the pacemaker (PMID:15071099). In immunity, VIP-VPAC2 signaling maintains the Th2/Th1 cytokine balance by inducing the transcription factors c-Maf and JunB to drive IL-4/IL-5 production, and supports regulatory T cell abundance and function (PMID:11698667, PMID:15187104, PMID:25305591). The receptor couples to cAMP/PKA but also engages cAMP-independent, PKC-dependent (neuroprotection) and PI3Kγ-WAVE2-actin (tumor cell migration) outputs, and mediates lipolysis, thalamic and hippocampal synaptic modulation, neurite/neurogenesis control, and vasodilation (PMID:15872042, PMID:36237322, PMID:15514088, PMID:16641377, PMID:15935995, PMID:19650041, PMID:15959462). Receptor activity is shaped by IC3-loop and transmembrane residues required for G-protein coupling (PMID:15821106, PMID:11498510), by ligand-selectivity determinants in the N-terminal ectodomain (PMID:10556928, PMID:10801840), and by homologous desensitization via GRK2 phosphorylation—augmented by PKA, cross-inhibited by M3/PKC/RKIP, and dependent on caveolin-1 (PMID:18077607, PMID:17170028, PMID:23499767). VPAC2 traffics to the plasma membrane and to primary cilia via a C-terminal RDYR signal recognized by Tubby, the BBSome, and Arl6 (PMID:23862016). VIPR2 copy-number gain at 7q36.3 increases receptor transcription and cAMP signaling in patient lymphocytes and, in BAC transgenic mice acting through dopaminoceptive neurons, drives schizophrenia-related developmental, dopaminergic, and behavioral deficits (PMID:21346763, PMID:31444475).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1999 Medium

    Establishing the gene's structure and ligand-selectivity architecture was the prerequisite for understanding how VPAC2 discriminates VIP from PACAP and where it sits in the genome.

    Evidence Genomic clone characterization mapping VIPR2 to 7q36.3, plus VPAC2/PAC1 and VPAC1/VPAC2 chimeric receptor binding/cAMP assays

    PMID:10481065 PMID:10491203 PMID:10556928

    Open questions at the time
    • No structural model of the active ligand-receptor complex
    • Selectivity mapped by domain swaps without residue-level resolution in these studies
  2. 2000 High

    Defining the ligand and receptor residues that govern VPAC2 binding and activation answered how the receptor is selectively engaged and enabled selective pharmacological tools.

    Evidence Alanine scanning of VIP and IC3/transmembrane mutagenesis (R172, K179, N216, IC3 residues) with binding, cAMP, Ca2+, phosphorylation and internalization assays in heterologous cells

    PMID:10801840 PMID:11498510 PMID:15821106 PMID:16650965

    Open questions at the time
    • No co-crystal/cryo-EM structure
    • Coupling to non-Gs pathways at residue level incompletely mapped
  3. 2002 High

    Knockout of Vipr2 answered whether the receptor is required for the circadian clock, establishing it as essential for sustained SCN rhythmicity and clock-gene expression.

    Evidence Vipr2-null mice with behavioral monitoring and SCN clock-gene in situ/Northern analysis

    PMID:12086606

    Open questions at the time
    • Did not resolve single-cell versus circuit-level requirement
    • Mechanism of intercellular coupling not defined here
  4. 2003 High

    Electrophysiology in null and antagonist-treated slices answered whether VPAC2 mediates VIP's acute neuronal actions and the firing-rate rhythm, establishing a cellular basis for its clock role.

    Evidence SCN slice recording from Vipr2-/- and wild-type mice with selective VPAC2 agonist/antagonist

    PMID:12542655

    Open questions at the time
    • Did not link firing changes to molecular oscillator at single-cell level
  5. 2004 High

    These studies answered how VPAC2 controls clock function beyond rhythm maintenance — gating photic input — and how it shapes adaptive immunity by setting the Th2/Th1 balance via specific transcription factors.

    Evidence pERK/c-FOS immunohistochemistry under light pulses in Vipr2-/- SCN; transcription factor (c-Maf, JunB) analysis in CD4 T cells from transgenic/KO/WT mice

    PMID:15071099 PMID:15187104

    Open questions at the time
    • Downstream effectors linking VPAC2-cAMP to ERK gating not defined
    • Direct cis-regulatory targets of c-Maf/JunB at IL-4/IL-5 not mapped here
  6. 2005 High

    Subtype-selective pharmacology and KO revealed VPAC2 uses divergent downstream pathways — cAMP-independent PKC for neuroprotection and PKA for synaptic enhancement — broadening the model beyond a single Gs-cAMP output.

    Evidence Vipr2-/- mice and selective agonists/antagonists with PKC/PKA inhibitors in excitotoxicity, hippocampal field recording, lipolysis and thalamic recording paradigms

    PMID:15514088 PMID:15821106 PMID:15872042 PMID:15935995 PMID:16641377 PMID:16709822

    Open questions at the time
    • Molecular basis of cAMP-independent PKC coupling unresolved
    • Splice-variant dominant-negative mechanism shown only in transfection
  7. 2006 High

    Smooth-muscle studies answered how VPAC2 signaling is terminated and cross-regulated, defining GRK2-mediated homologous desensitization and its inhibition by M3/PKC/RKIP cross-talk.

    Evidence RKIP(S153A) and GRK2 mutant expression, co-IP, phosphorylation and internalization assays in smooth muscle cells

    PMID:17170028

    Open questions at the time
    • Generalizability beyond gastric smooth muscle untested
    • In vivo relevance of cross-talk not demonstrated
  8. 2008 High

    PKA was shown to amplify GRK2-mediated desensitization and single-cell imaging confirmed VPAC2 is required for synchronous oscillator coupling, refining the desensitization and circadian-coupling models.

    Evidence GRK2(S685A) mutagenesis with cAMP/desensitization assays; Per1-GFP live confocal imaging in Vipr2-/- and antagonist-treated SCN slices

    PMID:18077607 PMID:18554318

    Open questions at the time
    • Coupling mechanism (which signal synchronizes cells) not fully resolved
  9. 2013 High

    These studies answered where VPAC2 is trafficked and how its surface behavior is modulated, defining ciliary targeting via an RDYR/BBSome pathway, caveolin-1-dependent internalization, and RAMP interactions.

    Evidence C-terminal/RDYR mutagenesis with Tubby/BBSome/Arl6 knockdown and ciliary imaging; caveolin-1 siRNA/KO and RAMP co-transfection with surface expression and G-protein assays

    PMID:22946657 PMID:23499767 PMID:23862016

    Open questions at the time
    • Functional consequence of ciliary versus plasma-membrane signaling not resolved
    • RAMP modulation shown only in heterologous cells
  10. 2019 High

    Patient lymphocyte and BAC transgenic studies answered whether VIPR2 copy-number gain is causally pathogenic, establishing increased VPAC2-cAMP signaling in dopaminoceptive neurons as the disease-relevant mechanism.

    Evidence cAMP/transcription assays in patient lymphocytes; conditional VIPR2 BAC transgenic mouse with Drd1a-Cre intersectional rescue and behavioral/dopaminergic readouts

    PMID:21346763 PMID:25575489 PMID:31444475

    Open questions at the time
    • Mechanism linking elevated cAMP to D2 receptor abnormality unresolved
    • Human causal evidence remains correlative at cellular level
  11. 2020 High

    Intersectional genetics resolved VPAC2-expressing cells as an autonomous, functionally powerful pacemaker subset, and additional KO studies extended VPAC2's roles to neurite outgrowth and refractive (myopia) control.

    Evidence VPAC2-Cre cell-type-specific CK1ε/Bmal1 deletion with behavior and TTFL imaging; cortical neuron neurite assays with PKA dissection; Vipr2-KO with retinal scRNA-seq, ERG and refraction

    PMID:32581681 PMID:32636383 PMID:33234609 PMID:33318135

    Open questions at the time
    • How VPAC2-cell intrinsic clock entrains the broader circuit not fully defined
    • Bipolar-cell signaling pathway to refractive development unmapped
  12. 2022 Medium

    Tumor cell studies answered how VPAC2 drives migration, defining a PI3Kγ-PIP3-WAVE2-Rac-actin pathway distinct from canonical cAMP signaling.

    Evidence VIPR2 silencing/overexpression with PI3K activity, PIP3 imaging, WAVE2-ARP3-actin co-IP and migration assays in breast cancer cells

    PMID:36237322

    Open questions at the time
    • G-protein link between VPAC2 and PI3Kγ not defined
    • Single cell-line context, in vivo metastasis untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How VPAC2 selects among its divergent effector pathways (Gs-cAMP/PKA, PKC, PI3Kγ) in a tissue- and ligand-specific manner, and the structural basis of biased signaling and ciliary versus surface function, remains unresolved.
  • No active-state structure of VPAC2
  • Determinants of pathway bias across tissues unknown
  • Functional role of ciliary localization in vivo undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005929 cilium 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-9909396 Circadian clock 3
Partners
CAV1GRK2PACAPRAMP1RAMP2RAMP3RKIPVIP

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 VPAC2 receptor (encoded by Vipr2) is essential for circadian function in the mouse SCN: Vipr2-/- mice cannot sustain circadian rhythms of rest/activity behavior, fail to show circadian expression of core clock genes mPer1, mPer2, and mCry1 and the clock-controlled gene AVP in the SCN, and fail to show acute induction of mPer1 and mPer2 by nocturnal illumination. Vipr2 null mouse knockout; behavioral monitoring; clock gene expression analysis by in situ hybridization/Northern blot Cell High 12086606
2003 VPAC2 receptor is necessary for the major part of the electrophysiological actions of VIP on SCN neurons in vitro: fewer SCN cells from Vipr2-/- mice responded to VIP and the VPAC2-selective agonist Ro 25-1553; VIP-evoked responses in control SCN neurons were attenuated by the selective VPAC2 antagonist PG 99-465. Additionally, the midday peak in SCN electrical firing rate rhythm was lost in Vipr2-/- mice and mimicked in controls by chronic VPAC2 antagonist treatment. Electrophysiological recording of SCN neurons in brain slices from Vipr2-/- and wild-type mice; pharmacological blockade with selective VPAC2 agonist and antagonist The European journal of neuroscience High 12542655
2004 In Vipr2-/- mice, photic gating of input to the SCN is abolished: spontaneous circadian variation in pERK and c-FOS is absent, and light pulses given during both subjective day and subjective night robustly increase pERK and c-FOS (versus only subjective night in wild-type), indicating that VPAC2 signaling is required for temporal gating of photic input to the SCN circadian pacemaker. Immunohistochemical detection of pERK and c-FOS in Vipr2-/- and wild-type SCN under LD and DD conditions with light pulse experiments The Journal of neuroscience High 15071099
2000 Overexpression of the human VPAC2 receptor in the SCN shortens the circadian period in constant darkness and accelerates resynchronization after an 8-h advance of the LD cycle, demonstrating that the level of VPAC2R expression directly influences the period and photic entrainment of the circadian clock. Transgenic mice overexpressing human VPAC2R from a YAC construct; wheel-running behavior monitoring in LD and constant darkness Proceedings of the National Academy of Sciences of the United States of America High 11027354
2001 Loss of VPAC2R in mice shifts T cell cytokine balance: VPAC2R-null mice show enhanced delayed-type hypersensitivity with increased IL-2 and IFN-γ (Th1 cytokines) and reduced IL-4 (Th2 cytokine) from splenic CD4+ T cells, and markedly lower IgE anti-hapten and cutaneous anaphylaxis, demonstrating that VIP-VPAC2R signaling normally maintains Th2/Th1 cytokine ratio. Vipr2-/- null mouse; hapten-evoked DTH assay; splenic CD4+ T cell cytokine production; serum Ig measurement Proceedings of the National Academy of Sciences of the United States of America High 11698667
2004 VIP binding to VPAC2 on CD4 T cells specifically induces up-regulation of the Th2-type transcription factors c-Maf and JunB (but not GATA3, T-bet, or NFATc), which leads to enhanced IL-4 and IL-5 production, establishing the molecular mechanism by which VPAC2 promotes Th2 differentiation. Analysis of transcription factor mRNA, protein and activity in TCR-stimulated CD4 T cells from VPAC2 transgenic, knockout, and wild-type mice; IL-4 and IL-5 measurement Journal of immunology High 15187104
2005 VIP-VPAC2 signaling is required for SCN cellular rhythmicity: in Vipr2-/- mice, only a small minority of SCN cells exhibit circadian firing patterns; exogenous GRP can promote SCN cellular rhythms in Vipr2-/- slices via BB2 receptors, while BB2 receptor blockade in wild-type mice suppresses neuronal oscillations only when VPAC2 receptors are also blocked. Electrophysiological recording of individual SCN neurons in brain slices from Vipr2-/- and wild-type mice; pharmacological application of GRP and BB2/VPAC2 receptor antagonists The Journal of neuroscience High 16319315
2007 VPAC2R-null mice lacking a functional SCN clock retain strongly rhythmic hepatic clock gene expression (advanced in phase), entrained by food intake timing rather than light; both genotypes develop food-anticipatory activity rhythms under restricted feeding, demonstrating that VPAC2-dependent SCN function is not required for food-entrainable peripheral oscillator function. Vipr2-/- mice; wheel-running, corticosterone secretion, hepatic clock gene expression under normal and restricted feeding regimens The Journal of neuroscience High 17442819
2007 In Vipr2-/- mice and VIP-deficient mice, daily metabolic and feeding rhythms are advanced (peak in late day rather than early night) under LD conditions, and are abolished under constant light, demonstrating that VIP-VPAC2 signaling controls temporal organization of metabolism and feeding behavior. Metabolic monitoring (indirect calorimetry), feeding behavior, and wheel-running in Vipr2-/- and VIP-deficient mice under LD and constant light American journal of physiology. Regulatory, integrative and comparative physiology High 18032467
2007 In gastric smooth muscle, VPAC2 receptor desensitization is mediated exclusively by GRK2: VIP induces GRK2-mediated phosphorylation of VPAC2, followed by internalization and desensitization; PKA-mediated phosphorylation of GRK2 at Ser685 augments its kinase activity and Gβγ binding, enhancing VPAC2 receptor phosphorylation, internalization, and desensitization. Expression of kinase-deficient GRK2(K220R) and PKA-site deficient GRK2(S685A) mutants; PKA inhibitor (PKI); 125I-VIP binding; receptor biotinylation; adenylyl cyclase activity and cAMP assays in smooth muscle cells American journal of physiology. Cell physiology High 18077607
2006 Cross-regulation of VPAC2 receptor desensitization by M3 muscarinic receptors: ACh activation of M3 receptors inhibits GRK2-mediated VPAC2 receptor phosphorylation, internalization and desensitization via PKC-mediated phosphorylation of RKIP at Ser153, which causes RKIP to dissociate from Raf-1 and instead bind and inhibit GRK2. In muscle cells expressing RKIP(S153A), this cross-regulatory mechanism is abolished. PKC inhibitors; RKIP(S153A) mutant expression in smooth muscle cells; RKIP-GRK2 and RKIP-Raf association by co-IP; VPAC2 phosphorylation, internalization, ERK1/2 activity assays American journal of physiology. Gastrointestinal and liver physiology High 17170028
2008 In individual SCN neurons from Vipr2-/- mice, fewer cells express detectable Per1-driven GFP rhythms, the oscillation amplitude is significantly lower, and cells are poorly synchronized with each other compared with wild-type; pharmacological VPAC2 receptor blockade in wild-type SCN partially mimics the Vipr2-/- phenotype, demonstrating that VPAC2 intercellular signaling is required for robust, synchronous clock gene oscillations at the single-cell level. Real-time confocal live imaging of destabilized GFP driven by Per1 in SCN-containing brain slices from Vipr2-/- and wild-type mice; VPAC2 pharmacological blockade Journal of neurochemistry High 18554318
2013 VPAC2 receptor interacts physically with all three RAMPs (RAMP1, RAMP2, RAMP3), enhancing their cell surface expression; this VPAC2-RAMP interaction modulates G-protein coupling in an agonist-specific manner, though cAMP production is not affected. Co-transfection of VPAC2 with RAMPs in HEK293S and CHO-K1 cells; ELISA for cell-surface RAMP/receptor expression; GTPγS binding to Gs, Gi, G12, Gq; cAMP assays British journal of pharmacology Medium 22946657
2013 VPAC2 localizes to primary cilia in neurons and glial cells of multiple brain regions including the SCN and thalamus; the C-terminus of VPAC2 is both necessary and sufficient for ciliary targeting, with a tetrapeptide RDYR motif serving as the ciliary targeting signal; ciliary targeting requires Tubby, the BBSome, and the BBSome-targeting factor Arl6. Endogenous VPAC2 immunofluorescence in brain sections; C-terminus deletion/truncation constructs; RDYR motif mutagenesis; knockdown of Tubby, BBSome subunits, and Arl6 Biology open High 23862016
2005 VPAC2 receptors mediate the PKC-dependent neuroprotective effects of VIP against neonatal excitotoxic brain lesions: VIP effects were mimicked by VPAC2 agonists and PHI but not VPAC1 agonists or PACAP; neuroprotection was lost in Vipr2-/- mice; protection is independent of cAMP and mediated by protein kinase C. Vipr2-/- mice and pharmacological agonist/antagonist approach in the ibotenate neonatal excitotoxicity mouse model; in situ hybridization for VPAC2 mRNA; VIP-specific binding assays The Journal of pharmacology and experimental therapeutics High 15872042
2004 VPAC2 receptor activation mediates lipolysis in primary rat adipocytes: VPAC2-selective agonists (Hexa-VIP(1-28) and Ro25-1553) mimicked PACAP38/VIP-induced glycerol release, while the VPAC2 antagonist PG99-465 right-shifted dose-response curves; PAC1-R and VPAC1-R antagonists/agonists had no effect on lipolysis, demonstrating VPAC2 as the sole mediator. RT-PCR for receptor expression; glycerol release assay with selective agonists (Ro25-1553, Hexa-VIP) and antagonists (PACAP(6-38), PG97-269, PG99-465) in primary rat adipocytes Endocrinology High 15514088
2009 VIP acting via VPAC2 receptors is trophic for proliferating postnatal nestin-positive dentate neural stem/progenitor cells (NSPCs) and shifts the fate of symmetrically dividing NSPCs toward a nestin-only phenotype; selective VPAC1 activation instead directs NSPCs toward granule cell neurogenesis; Vipr2-/- mice show reduced progeny survival and dentate neurogenesis with a specific reduction of type 2 nestin-positive precursors in vivo. Selective receptor agonists on postnatal dentate NSPCs; BrdU/immunofluorescence; Vipr2-/- mouse in vivo analysis of neurogenesis Stem cells High 19650041
2005 VIP enhances hippocampal CA1 synaptic transmission via both VPAC1 and VPAC2 receptors; VPAC2-mediated actions are specifically dependent on PKA activity (blocked by H-89 but not GF109203X), whereas VPAC1-mediated actions require PKC activity. Extracellular field potential recording in rat hippocampal slices; selective VPAC2 agonist RO 25-1553 and antagonist PG 99-465; PKA inhibitor H-89 and PKC inhibitor GF109203X Brain research Medium 15935995
2005 VPAC2 receptor activation in the spinal cord contributes to p38 MAP kinase phosphorylation and behavioral reflex sensitization in neuropathic pain: a VPAC2 agonist enhanced p38 phosphorylation and caused behavioral sensitization in naïve animals, blocked by a p38 inhibitor; NMDA/VPAC2/NK2 receptor antagonists and the glial inhibitor propentofylline all reduced p38/p42/44 activation after nerve injury. Intrathecal VPAC2 agonist/antagonist administration; p38 and p42/44 phosphorylation assays; behavioral nociceptive tests in nerve constriction injury model Molecular and cellular neurosciences Medium 16202621
2006 VPAC2 receptor in porcine basilar arteries is located in the outer smooth muscle layers and mediates neurally-evoked (electrical stimulation at 20 Hz) vasodilation independently of nitric oxide synthase and the endothelium; VPAC2 antagonist PG-99-465 attenuated the vasodilatory response to electrical stimulation. Immunocytochemistry for receptor localization; pharmacological vasodilation assays with L-NAME, endothelial denudation, and selective VPAC2 antagonist/agonist in porcine basilar artery preparations; RT-PCR Journal of cerebral blood flow and metabolism Medium 15959462
2005 VPAC2 receptor activation in SCN neurons enhances the hyperpolarization-activated mixed cation current (Ih) via cAMP, causing membrane depolarization of thalamocortical relay neurons and attenuation of intrathalamic rhythmic activities; these effects are absent in Vipr2-/- mice. Intracellular recordings in thalamic slices from wild-type and Vipr2-/- mice; VIP and PACAP application; pharmacological cAMP manipulation Journal of neurophysiology High 16641377
2009 VPAC2 receptor activation in the subparaventricular zone (SPZ) mediates both postsynaptic depolarization via a nonselective cationic conductance and presynaptic enhancement of GABA release from SCN terminals; these effects are mimicked by the selective VPAC2 agonist BAY 55-9837 and partially blocked by VIP(6-28). Patch-clamp recording in rat brain slices of SPZ; selective VPAC2 agonist BAY 55-9837; VIP receptor antagonist; TTX-resistant current measurements; mIPSC frequency analysis Journal of neurophysiology Medium 19571188
2009 VPAC2 is the sole VIP/PACAP receptor expressed in MC3T3-E1 osteoblastic cells; PACAP/VIP stimulate cAMP accumulation and IL-6 release exclusively through VPAC2, and VPAC2 siRNA knockdown abolishes both responses; VPAC2-cAMP signaling suppresses osteoblastic differentiation (reduces alkaline phosphatase mRNA). RT-PCR; VPAC2 siRNA knockdown; cAMP assay; IL-6 ELISA; alkaline phosphatase mRNA quantification in MC3T3-E1 cells Journal of cellular physiology Medium 19496170
2011 VPAC2 activation drives reactive astrocytosis: selective VPAC2 agonist Ro25-1553 induces reactive morphological changes in cultured astrocytes (polygonal to stellate) and increases cell surface expression of glutamate transporters GLAST and GLT-1; VPAC2 is transiently expressed in reactive astrocytes around brain injury sites in vivo. Cold injury brain lesion model in mice; immunohistochemistry; primary cultured astrocytes treated with dbcAMP and VPAC2 agonist; glutamate transporter surface expression assay Brain research Medium 21281617
2013 Caveolin-1 is required for VPAC2 receptor internalization and desensitization in gastric smooth muscle: VIP stimulates tyrosine phosphorylation of caveolin-1 via Src kinase; disruption of caveolae by methyl-β-cyclodextrin, caveolin-1 siRNA knockdown, or caveolin-1 KO mice all significantly attenuate VPAC2 receptor internalization and desensitization. Methyl-β-cyclodextrin caveolae disruption; caveolin-1 siRNA; caveolin-1 KO mice; 125I-VIP binding; receptor biotinylation; adenylyl cyclase activity; muscle strip relaxation assays Peptides High 23499767
2005 The VPAC2 receptor IC3 loop conserved residues are required for G-protein coupling and receptor regulation: L310 mutation reduces Gαs-coupled adenylyl cyclase efficacy by 75% without affecting Gα16-coupled Ca2+ signaling; R325 and K328 mutations reduce Ca2+ and cAMP responses; combined amino- and carboxy-terminal IC3 mutations generate a fully inactive receptor lacking phosphorylation and internalization, both of which are directly correlated with receptor activation efficacy. Point mutagenesis of IC3 loop residues; expression in CHO cells stably transfected with Gα16 and aequorin; adenylyl cyclase activity; Ca2+ measurement; receptor phosphorylation and internalization assays Journal of molecular endocrinology High 15821106
2006 The conserved Asn216 in TM3 of VPAC2 is important for receptor activation: N216Q mutation reduces VIP stimulation of adenylyl cyclase, receptor phosphorylation and internalization, indicating a role in G-protein activation analogous to the equivalent Asn229 in VPAC1. Conservative mutagenesis N216Q in VPAC2; adenylyl cyclase activity; receptor phosphorylation and internalization assays in CHO cells Cellular signalling Medium 16650965
2001 Conserved basic residues R172 and K179 in the second transmembrane helix of VPAC2 are required for receptor activation: R172 mutations reduce VIP potency by 20–500-fold; K179I mutation renders the receptor inactive to VIP; substituting Asp3 of VIP with Asn or Gln markedly improved potency at R172 mutants, suggesting R172 and VIP Asp3 come into close proximity in the active ligand-receptor complex. Site-directed mutagenesis (R172L, R172Q, K179Q, K179I); adenylyl cyclase assays with VIP and analogs; expressed in COS cells British journal of pharmacology Medium 11498510
1999 Ligand selectivity of VPAC2 versus PAC1 receptors is determined primarily by the amino-terminal extracellular domain: chimeric receptor experiments show the N-terminal extracellular domain of each receptor determines VIP vs. PACAP-38 selectivity; substitution of increasing portions of VPAC2 sequence into a PAC1-N-terminal-domain chimera decreases VIP potency while increasing helodermin potency, indicating additional receptor domains differentially modulate VIP and helodermin (but not PACAP) binding. Construction and expression of VPAC2/PAC1 chimeric receptors in COS7 cells; 125I-PACAP-27 binding; cAMP assays with VIP, PACAP-38, PACAP-27, helodermin British journal of pharmacology Medium 10556928
1999 The N-terminal extracellular domain of VPAC1 determines the selectivity of a VPAC1-selective agonist and antagonist; efficient receptor activation by selective VIP1 agonist additionally requires the first extracellular loop and distal VPAC1 receptor domains, as replacement of EC1 in VPAC1 by its VPAC2 counterpart markedly reduces maximal response. VPAC1/VPAC2 chimeric receptors evaluated for binding and functional activation in transfected cells European journal of biochemistry Medium 10491203
2000 Alanine scanning of VIP identifies residues Thr11, Tyr22, and Asn28 as uniquely important for binding/activation of VPAC2 (vs. VPAC1): substitution of Thr11 and Asn28 selectively increases Ki for VPAC2 binding; substitution of Tyr22 selectively increases EC50 for VPAC2 adenylyl cyclase activation. Combining three mutations (Ala11,22,28) yields the first highly selective (>1000-fold) VPAC1 agonist. Solid-phase synthesis of alanine-scan VIP analogs; binding (Ki) and adenylyl cyclase activation (EC50) in cell membranes expressing recombinant VPAC1 or VPAC2; 3D molecular modeling The Journal of biological chemistry High 10801840
2007 VPAC2 receptor VIPR2 transcription and cyclic-AMP signaling are significantly increased in cultured lymphocytes from schizophrenia patients with microduplications of 7q36.3 containing VIPR2, implicating increased VPAC2 signaling as the functional consequence of gene copy number gain. cAMP signaling assays and VIPR2 transcription measurement in cultured lymphocytes from patients with confirmed 7q36.3 microduplications versus controls Nature Medium 21346763
2019 VIPR2 microduplication in a BAC transgenic mouse model recapitulates schizophrenia-related phenotypes: increased striatal cAMP/PKA signaling, disrupted early postnatal striatal development, dopamine D2 receptor abnormality, and cognitive/sensorimotor gating/social behavioral deficits; genetic removal of VIPR2 transgene in dopaminoceptive neurons (Drd1a-Cre) rescued D2 receptor abnormality and multiple behavioral deficits, implicating VIPR2 overexpression in dopaminoceptive neurons as pathogenic. Conditional VIPR2 BAC transgenic mouse; Drd1a-Cre intersectional rescue; cAMP/PKA signaling assays; dopamine D2 receptor measurement; behavioral testing Molecular psychiatry High 31444475
2020 VIP/VPAC2-expressing cells together constitute a pacemaker hub in the SCN circuit: using intersectional genetics and real-time imaging, VIP-expressing and VPAC2-expressing cells are neurochemically and electrophysiologically distinct but together control de novo rhythmicity, setting ensemble period and phase with circuit-level spatiotemporal complexity. Intersectional genetics (VIP-Cre and VPAC2 reporter mice); real-time bioluminescence imaging; electrophysiology of defined cell populations Nature communications High 32636383
2020 VPAC2-expressing cells contribute autonomously to SCN timekeeping: lengthening the intrinsic TTFL period of VPAC2-expressing cells (by CK1ε deletion) lengthens behavioral circadian period; abrogation of circadian competence in VPAC2 cells (Bmal1 deletion) severely disrupts circadian behavioral rhythms and SCN TTFL timekeeping, demonstrating that VPAC2-expressing cells are a functionally powerful subset within the SCN circuit. Intersectional genetics in VPAC2-Cre mice: cell-type-specific deletion of CK1ε and Bmal1; wheel-running behavior; bioluminescent TTFL imaging in SCN slices The Journal of neuroscience High 33234609
2020 VPAC2 receptor activation impairs neurite outgrowth in cortical neurons via a PKA-dependent mechanism: VIP and the VPAC2-selective agonist Ro25-1553 reduced total numbers and lengths of dendrites and axons; these effects were blocked by the VPAC2 antagonist PG99-465, absent in Vipr2-/- neurons, and blocked by the PKA inhibitor H-89 but not by PKC or MEK inhibitors. Primary mouse cortical neuron cultures; selective agonist Ro25-1553 and antagonist PG99-465; Vipr2-/- neurons; PKA (H-89), PKC (GF109203X), and MEK (U0126) inhibitors; neurite morphometry Frontiers in neuroscience High 32581681
2020 Loss of VIPR2 function in mice causes myopia: Vipr2-KO mice show significant myopic refraction shift; VIPR2 is expressed in retinal bipolar cells; VIPR2 agonist Ro25-1553 inhibited form deprivation myopia, while antagonist PG99-465 induced relative myopia; Vipr2-KO mice show enlarged b-wave amplitudes consistent with altered bipolar cell function. Vipr2-KO mice; retinal single-cell transcriptome sequencing for cell-type expression; pharmacological agonist/antagonist administration; electroretinography; refraction measurement Journal of medical genetics High 33318135
2022 VIP-VIPR2 signaling controls tumor cell migration via PI3Kγ-mediated synthesis of PI(3,4,5)P3, which promotes membrane localization of WAVE2 and Rac-mediated actin nucleation for lamellipodium formation: VIPR2 co-localizes with WAVE2 at lamellipodia; VIPR2 silencing suppresses VIP-induced migration and lamellipodium extension; PI3Kγ inhibitor blocks VIPR2-overexpressing cell migration; VIPR2 knockdown reduces WAVE2-ARP3-actin interactions. VIPR2 siRNA silencing and stable overexpression in MDA-MB-231 and MCF-7 cells; PI3K activity assay; PI(3,4,5)P3 membrane localization imaging; WAVE2-ARP3-actin co-IP; PI3Kγ inhibitor; wound healing/migration assay Frontiers in oncology Medium 36237322
2003 VPAC2 receptor is expressed by immature pancreatic epithelial cells between embryonic days 12–16 and mediates VIP/PACAP-induced survival, proliferation, and increased endocrine cell number in embryonic pancreas in vitro. Embryonic pancreas organ culture with VIP/PACAP; RT-PCR for VPAC2 expression during development; cell survival and proliferation assays; endocrine cell counting Diabetes Medium 12502497
2014 VPAC2 receptor deficiency in mice exacerbates EAE: Vipr2-/- mice show enhanced neuroinflammation, increased Th1/Th17 cytokines (IFN-γ, IL-17), reduced anti-inflammatory cytokines (IL-10, TGFβ, IL-4), and strikingly reduced abundance and proliferative index of CD4+CD25+FoxP3+ Tregs in lymph nodes, thymus, and CNS; in vitro suppressive activity of Tregs from VPAC2-deficient mice is impaired. Vipr2-/- mice in MOG35-55 EAE model; histopathology; cytokine measurement (ELISA/flow); Treg frequency by FACS; in vitro Treg suppression assay Brain, behavior, and immunity High 25305591
2017 VPAC2 receptor deficiency impairs extinction of cued fear memory and alters dendritic morphology in the prelimbic and infralimbic cortices: Vipr2-/- mice show normal fear acquisition and expression but impaired cued fear extinction; prelimbic cortex neurons show reduced cell body size and reduced total dendritic branch number and length; proximal dendritic material in infralimbic cortex is increased in Vipr2-/- mice. Pavlovian fear conditioning and extinction in Vipr2-/- and wild-type mice; Golgi staining and morphological analysis of PrL and IL cortex neurons; Sholl analysis Neurobiology of learning and memory Medium 29030297
2007 VPAC2 receptor stimulation inhibits HIV-1 integration into host DNA: daily VPAC2 agonist treatment (but not VPAC1 or PAC1 agonists) caused up to 90% inhibition of HIV-1 productive infection in cell lines and PBMCs without affecting cell surface co-receptors, apoptosis, viral entry, or reverse transcription, implicating the integration step as the target. VPAC2/VPAC1/PAC1-selective agonist treatment of cell lines and PBMCs; HIV-1 infection assays; entry/reverse transcription/integration assays Virology Medium 17257640
2015 Postnatal overactivation of VPAC2 receptor (Ro 25-1553, P1–P14) reduces synaptophysin and PSD-95 protein levels specifically in the prefrontal cortex (not hippocampus) and disrupts prepulse inhibition of acoustic startle in adult mice, modeling the developmental consequences of VIPR2 overdosage. Postnatal subcutaneous Ro 25-1553 in C57BL/6 mice; Western blot for synaptic proteins; PPI of acoustic startle; open field; social interaction; fear conditioning Psychopharmacology Medium 25575489
1999 The human VIPR2 gene spans 117 kb, is encoded by 13 exons, with the initiator codon in exon 1, the stop codon and poly-adenylation signal in exon 13, an 80% GC-rich 5' UTR, intron sizes ranging from 68 bp to 45 kb, and maps to chromosome 7q36.3. Gene structure characterization from genomic clones; exon-intron boundary sequencing; promoter region analysis FEBS letters Medium 10481065
2006 A short-deletion (SD) splice variant of mouse VPAC2 lacking 14 amino acids at the end of the last transmembrane domain binds VIP with similar affinity to wild-type VPAC2 but lacks signaling capacity for adenylyl cyclase; cotransfection of SD and wild-type VPAC2 diminishes VIP enhancement of IL-4 production by preventing nuclear accumulation of c-Maf and JunB. Transfection of WT and SD VPAC2 constructs in Th2 cell line; IL-4 measurement; nuclear transcription factor level assays; endogenous VIP neutralization Journal of immunology Medium 16709822

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 The VPAC(2) receptor is essential for circadian function in the mouse suprachiasmatic nuclei. Cell 461 12086606
2011 Copy number variants in schizophrenia: confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications. The American journal of psychiatry 357 21285140
2011 Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia. Nature 261 21346763
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
2003 The mouse VPAC2 receptor confers suprachiasmatic nuclei cellular rhythmicity and responsiveness to vasoactive intestinal polypeptide in vitro. The European journal of neuroscience 124 12542655
2005 Gastrin-releasing peptide promotes suprachiasmatic nuclei cellular rhythmicity in the absence of vasoactive intestinal polypeptide-VPAC2 receptor signaling. The Journal of neuroscience : the official journal of the Society for Neuroscience 101 16319315
2001 Enhanced delayed-type hypersensitivity and diminished immediate-type hypersensitivity in mice lacking the inducible VPAC(2) receptor for vasoactive intestinal peptide. Proceedings of the National Academy of Sciences of the United States of America 101 11698667
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
2000 Overexpression of the human VPAC2 receptor in the suprachiasmatic nucleus alters the circadian phenotype of mice. Proceedings of the National Academy of Sciences of the United States of America 90 11027354
2015 Methylomic analysis of salivary DNA in childhood ADHD identifies altered DNA methylation in VIPR2. Journal of child psychology and psychiatry, and allied disciplines 89 26304033
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
2004 Aberrant gating of photic input to the suprachiasmatic circadian pacemaker of mice lacking the VPAC2 receptor. The Journal of neuroscience : the official journal of the Society for Neuroscience 87 15071099
2003 Distribution of the VPAC2 receptor in peripheral tissues of the mouse. Endocrinology 80 14617572
2007 Entrainment to feeding but not to light: circadian phenotype of VPAC2 receptor-null mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 73 17442819
2013 Receptor activity modifying proteins (RAMPs) interact with the VPAC2 receptor and CRF1 receptors and modulate their function. British journal of pharmacology 67 22946657
2007 Metabolic rhythm abnormalities in mice lacking VIP-VPAC2 signaling. American journal of physiology. Regulatory, integrative and comparative physiology 66 18032467
2000 Development of selective agonists and antagonists for the human vasoactive intestinal polypeptide VPAC(2) receptor. Peptides 66 11068102
2020 The VIP-VPAC2 neuropeptidergic axis is a cellular pacemaking hub of the suprachiasmatic nucleus circadian circuit. Nature communications 56 32636383
2008 Live imaging of altered period1 expression in the suprachiasmatic nuclei of Vipr2-/- mice. Journal of neurochemistry 55 18554318
2013 PACAP and VIP increase the expression of myelin-related proteins in rat schwannoma cells: involvement of PAC1/VPAC2 receptor-mediated activation of PI3K/Akt signaling pathways. Experimental cell research 53 24246222
2001 Expression and distribution of vasoactive intestinal polypeptide receptor VPAC(2) mRNA in human airways. Laboratory investigation; a journal of technical methods and pathology 53 11351046
2004 Transgenic approach reveals expression of the VPAC2 receptor in phenotypically defined neurons in the mouse suprachiasmatic nucleus and in its efferent target sites. The European journal of neuroscience 51 15090046
2007 Decreased VIP and VPAC2 receptor expression in the biological clock of the R6/2 Huntington's disease mouse. Journal of molecular neuroscience : MN 46 17478887
2004 Ageing and the diurnal expression of mRNAs for vasoactive intestinal peptide and for the VPAC2 and PAC1 receptors in the suprachiasmatic nucleus of male rats. Journal of neuroendocrinology 45 15344914
2003 Bronchodilation by an inhaled VPAC(2) receptor agonist in patients with stable asthma. Thorax 45 12612296
2005 Activation of p38 and p42/44 MAP kinase in neuropathic pain: involvement of VPAC2 and NK2 receptors and mediation by spinal glia. Molecular and cellular neurosciences 40 16202621
2004 c-Maf and JunB mediation of Th2 differentiation induced by the type 2 G protein-coupled receptor (VPAC2) for vasoactive intestinal peptide. Journal of immunology (Baltimore, Md. : 1950) 40 15187104
2014 VPAC2 (vasoactive intestinal peptide receptor type 2) receptor deficient mice develop exacerbated experimental autoimmune encephalomyelitis with increased Th1/Th17 and reduced Th2/Treg responses. Brain, behavior, and immunity 39 25305591
2003 Generation of highly selective VPAC2 receptor agonists by high throughput mutagenesis of vasoactive intestinal peptide and pituitary adenylate cyclase-activating peptide. The Journal of biological chemistry 39 12525492
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
2008 Behavioral responses of Vipr2-/- mice to light. Journal of biological rhythms 38 18487413
2003 Evidence for the involvement of VPAC1 and VPAC2 receptors in pressure-induced vasodilatation in rodents. The Journal of physiology 38 14578481
2005 VPAC2 receptors mediate vasoactive intestinal peptide-induced neuroprotection against neonatal excitotoxic brain lesions in mice. The Journal of pharmacology and experimental therapeutics 37 15872042
2002 Expression of VPAC2 receptor and PAC1 receptor splice variants in the trigeminal ganglion of the adult rat. Brain research. Molecular brain research 37 12225867
2012 PACAP causes PAC1/VPAC2 receptor mediated hypertension and sympathoexcitation in normal and hypertensive rats. American journal of physiology. Heart and circulatory physiology 36 22886412
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
2009 Daily rhythms and sex differences in vasoactive intestinal polypeptide, VIPR2 receptor and arginine vasopressin mRNA in the suprachiasmatic nucleus of a diurnal rodent, Arvicanthis niloticus. The European journal of neuroscience 35 19811536
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
2013 Stapled Vasoactive Intestinal Peptide (VIP) Derivatives Improve VPAC2 Agonism and Glucose-Dependent Insulin Secretion. ACS medicinal chemistry letters 31 24900623
2017 PAC1- and VPAC2 receptors in light regulated behavior and physiology: Studies in single and double mutant mice. PloS one 30 29155851
2004 VPAC2-R mediates the lipolytic effects of pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal polypeptide in primary rat adipocytes. Endocrinology 30 15514088
2009 Identification and characterization of a small molecule antagonist of human VPAC(2) receptor. Molecular pharmacology 29 19854890
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
2007 Phosphorylation of GRK2 by PKA augments GRK2-mediated phosphorylation, internalization, and desensitization of VPAC2 receptors in smooth muscle. American journal of physiology. Cell physiology 28 18077607
2019 Cross-talk between fetal membranes and visceral adipose tissue involves HMGB1-RAGE and VIP-VPAC2 pathways in human gestational diabetes mellitus. Acta diabetologica 27 30820673
2009 cAMP activation by PACAP/VIP stimulates IL-6 release and inhibits osteoblastic differentiation through VPAC2 receptor in osteoblastic MC3T3 cells. Journal of cellular physiology 27 19496170
2017 Impaired extinction of cued fear memory and abnormal dendritic morphology in the prelimbic and infralimbic cortices in VPAC2 receptor (VIPR2)-deficient mice. Neurobiology of learning and memory 26 29030297
2005 VIP enhances synaptic transmission to hippocampal CA1 pyramidal cells through activation of both VPAC1 and VPAC2 receptors. Brain research 26 15935995
2006 Engineering novel VPAC2-selective agonists with improved stability and glucose-lowering activity in vivo. The Journal of pharmacology and experimental therapeutics 23 17110523
2006 Cross-regulation of VPAC(2) receptor desensitization by M(3) receptors via PKC-mediated phosphorylation of RKIP and inhibition of GRK2. American journal of physiology. Gastrointestinal and liver physiology 23 17170028
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
2020 Dysfunction of VIPR2 leads to myopia in humans and mice. Journal of medical genetics 22 33318135
2017 VPAC1 and VPAC2 receptor activation on GABA release from hippocampal nerve terminals involve several different signalling pathways. British journal of pharmacology 22 28945273
2016 Copy Number Variants in Patients with Autism and Additional Clinical Features: Report of VIPR2 Duplication and a Novel Microduplication Syndrome. Molecular neurobiology 22 27796743
2013 Genetic susceptibility to refractive error: association of vasoactive intestinal peptide receptor 2 (VIPR2) with high myopia in Chinese. PloS one 22 23637909
2010 Region-specific changes in the immunoreactivity of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide receptors (VPAC2, and PAC1 receptor) in the aged rat brains. Brain research 22 20599818
1999 Domains determining agonist selectivity in chimaeric VIP2 (VPAC2)/PACAP (PAC1) receptors. British journal of pharmacology 22 10556928
2015 Constant light enhances synchrony among circadian clock cells and promotes behavioral rhythms in VPAC2-signaling deficient mice. Scientific reports 21 26370467
2011 Activation of the VIP/VPAC2 system induces reactive astrocytosis associated with increased expression of glutamate transporters. Brain research 21 21281617
2005 Modeling the VPAC2-activated cAMP/PKA signaling pathway: from receptor to circadian clock gene induction. Biophysical journal 21 16339878
2014 VPAC2 receptor expression in human normal and neoplastic tissues: evaluation of the novel MAB SP235. Endocrine connections 20 25504760
2009 Effects of VPAC2 receptor activation on membrane excitability and GABAergic transmission in subparaventricular zone neurons targeted by suprachiasmatic nucleus. Journal of neurophysiology 20 19571188
1999 Structure of the human VIPR2 gene for vasoactive intestinal peptide receptor type 2. FEBS letters 20 10481065
2015 Reductions in synaptic proteins and selective alteration of prepulse inhibition in male C57BL/6 mice after postnatal administration of a VIP receptor (VIPR2) agonist. Psychopharmacology 19 25575489
2012 Low-copy repeats at the human VIPR2 gene predispose to recurrent and nonrecurrent rearrangements. European journal of human genetics : EJHG 19 23073313
2010 The absence of VPAC2 leads to aberrant antibody production in Aspergillus fumigatus sensitized and challenged mice. Peptides 19 20923692
2005 Effect of inactivating mutations on phosphorylation and internalization of the human VPAC2 receptor. Journal of molecular endocrinology 19 15821106
2022 Alterations in Gut Microbiota and Upregulations of VPAC2 and Intestinal Tight Junctions Correlate with Anti-Inflammatory Effects of Electroacupuncture in Colitis Mice with Sleep Fragmentation. Biology 18 36101343
2004 Cytosolic Ca2+ responses to sub-picomolar and nanomolar PACAP in pancreatic beta-cells are mediated by VPAC2 and PAC1 receptors. Regulatory peptides 18 15518905
2001 Structural and functional identification of the pituitary adenylate cyclase-activating polypeptide receptor VPAC2 from the frog Rana tigrina rugulosa. Journal of molecular endocrinology 18 11564605
2020 Activation of the VPAC2 Receptor Impairs Axon Outgrowth and Decreases Dendritic Arborization in Mouse Cortical Neurons by a PKA-Dependent Mechanism. Frontiers in neuroscience 17 32581681
2014 A competitive PCR assay confirms the association of a copy number variation in the VIPR2 gene with schizophrenia in Han Chinese. Schizophrenia research 17 24794882
2013 Targeting of vasoactive intestinal peptide receptor 2, VPAC2, a secretin family G-protein coupled receptor, to primary cilia. Biology open 17 23862016
2010 Role of VPAC1 and VPAC2 in VIP mediated inhibition of rat pulmonary artery and aortic smooth muscle cell proliferation. Peptides 17 20452385
2006 Differential signaling of T cell generation of IL-4 by wild-type and short-deletion variant of type 2 G protein-coupled receptor for vasoactive intestinal peptide (VPAC2). Journal of immunology (Baltimore, Md. : 1950) 17 16709822
2003 Role for VPAC2 receptor-mediated signals in pancreas development. Diabetes 17 12502497
2022 Vasoactive intestinal peptide-VIPR2 signaling regulates tumor cell migration. Frontiers in oncology 16 36237322
2021 Probing the VIPR2 Microduplication Linkage to Schizophrenia in Animal and Cellular Models. Frontiers in neuroscience 16 34366784
2020 The Cell-Autonomous Clock of VIP Receptor VPAC2 Cells Regulates Period and Coherence of Circadian Behavior. The Journal of neuroscience : the official journal of the Society for Neuroscience 16 33234609
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
2004 Comparative efficacy of VIP and analogs on activation and internalization of the recombinant VPAC2 receptor expressed in CHO cells. Peptides 16 15572195
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
2001 Mutational analysis of the human vasoactive intestinal peptide receptor subtype VPAC(2): role of basic residues in the second transmembrane helix. British journal of pharmacology 16 11498510
2021 Generation of KS-133 as a Novel Bicyclic Peptide with a Potent and Selective VIPR2 Antagonist Activity that Counteracts Cognitive Decline in a Mouse Model of Psychiatric Disorders. Frontiers in pharmacology 15 34819858
2010 The absence of the VPAC(2) receptor does not protect mice from Aspergillus induced allergic asthma. Peptides 15 20226823
2021 Modified BuShenYiQi formula alleviates experimental allergic asthma in mice by negative regulation of type 2 innate lymphoid cells and CD4+ type 9 helper T cells and the VIP-VPAC2 signalling pathway. Pharmaceutical biology 14 34493162
2017 A novel selective VPAC2 agonist peptide-conjugated chitosan modified selenium nanoparticles with enhanced anti-type 2 diabetes synergy effects. International journal of nanomedicine 14 28356733
2006 Excitatory actions of vasoactive intestinal peptide on mouse thalamocortical neurons are mediated by VPAC2 receptors. Journal of neurophysiology 14 16641377
2006 VPAC2 receptor activation mediates VIP enhancement of population spikes in the CA1 area of the hippocampus. Annals of the New York Academy of Sciences 14 16888168
2000 IL-4 regulates VIP receptor subtype 2 mRNA (VPAC2) expression in T cells in murine schistosomiasis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 14 10783149
2000 Vasoactive intestinal peptide (VIP) receptor type 2 (VPAC2) is the predominant receptor expressed in human thymocytes. Annals of the New York Academy of Sciences 14 11193874
2019 Dosage sensitivity intolerance of VIPR2 microduplication is disease causative to manifest schizophrenia-like phenotypes in a novel BAC transgenic mouse model. Molecular psychiatry 13 31444475
2019 The myopia susceptibility locus vasoactive intestinal peptide receptor 2 (VIPR2) contains variants with opposite effects. Scientific reports 12 31796800
2013 Caveolae-dependent internalization and homologous desensitization of VIP/PACAP receptor, VPAC₂, in gastrointestinal smooth muscle. Peptides 12 23499767
2011 The VPAC2 agonist peptide histidine isoleucine (PHI) up-regulates glutamate transport in the corpus callosum of a rat model of amyotrophic lateral sclerosis (hSOD1G93A) by inhibiting caspase-3 mediated inactivation of GLT-1a. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 12 21730107
2007 HIV-1 integration is inhibited by stimulation of the VPAC2 neuroendocrine receptor. Virology 12 17257640
2006 Intein-mediated rapid purification and characterization of a novel recombinant agonist for VPAC2. Peptides 12 16500728
2022 Therapeutic potential of vasoactive intestinal peptide and its receptor VPAC2 in type 2 diabetes. Frontiers in endocrinology 11 36204104
2004 Hexanoylation of a VPAC2 receptor-preferring ligand markedly increased its selectivity and potency. Peptides 11 15063009

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