Affinage

AVP

Vasopressin-neurophysin 2-copeptin · UniProt P01185

Round 2 corrected
Length
164 aa
Mass
17.3 kDa
Annotated
2026-04-28
130 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AVP encodes the vasopressin-neurophysin 2-copeptin precursor, a nonapeptide hormone that signals through V1a (PLC/Ca²⁺/PKC), V1b (PLC/Ca²⁺/PKC), and V2 (adenylate cyclase/cAMP/PKA) receptor subtypes to regulate water and electrolyte homeostasis, HPA axis output, and innate immunity. In the kidney, V2 receptor activation drives AQP2 trafficking and apical Na⁺ channel opening for water and sodium reabsorption, while V1 receptor signaling mediates mesangial cell contraction, PGE₂ synthesis, and K⁺ secretion through BK channels; these pathways are counter-regulated by nucleotide/P2u-PKC, PGE₂-PKC→Gᵢ, CaSR-calmodulin, and apelin receptor systems (PMID:3394807, PMID:1313121, PMID:8594881, PMID:8764317, PMID:15253724, PMID:18032798, PMID:33436646). Proper precursor processing and secretion require both the vasopressin and neurophysin coding regions, and frameshift loss of neurophysin causes diabetes insipidus (PMID:9402088). Peripherally, AVP suppresses macrophage AHI1 expression, destabilizing Tyk2 via loss of OTUD1-mediated deubiquitination and attenuating type-I interferon antiviral signaling (PMID:35821088).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1984 High

    Identifying the receptor subtype mediating AVP-stimulated ACTH release resolved why V1 and V2 antagonists failed to fully block pituitary corticotrope activation, establishing the existence of a pharmacologically distinct third AVP receptor (later called V1b/V3).

    Evidence In vitro pharmacological antagonism assay on rat anterior pituitary segments with selective V1/V2 ligands, measuring ACTH by RIA

    PMID:6089144

    Open questions at the time
    • V1b receptor gene had not yet been cloned
    • downstream signaling cascade of V1b in corticotropes was not defined
  2. 1988 High

    Demonstrating that AVP causes mesangial cell contraction through V1-mediated intracellular Ca²⁺ mobilization from ER stores and extracellular Ca²⁺ influx established the dual-source Ca²⁺ mechanism underlying AVP's glomerular hemodynamic effects.

    Evidence Ca²⁺ imaging, ⁴⁵Ca²⁺ efflux, V1-selective antagonist, dantrolene and verapamil pharmacology in cultured mesangial cells

    PMID:3394807

    Open questions at the time
    • identity of the voltage-insensitive Ca²⁺ influx channel was unknown
    • relevance to intact glomerular filtration rate regulation not directly tested
  3. 1992 High

    Patch-clamp studies revealed that AVP acts via cAMP/PKA to recruit quiescent apical Na⁺ channels and increase their open probability in the collecting duct, distinguishing this mechanism from mineralocorticoid-driven de novo channel synthesis and explaining their synergism in sodium reabsorption.

    Evidence Electrophysiological patch-clamp and cAMP measurements in isolated perfused rat cortical collecting duct

    PMID:1313121

    Open questions at the time
    • molecular identity of the Na⁺ channel pool recruited by AVP was unclear
    • trafficking mechanism for channel insertion was not defined
  4. 1992 Medium

    Selective lesion of the lateral fimbria-fornix revealed that hippocampal efferents tonically suppress AVP mRNA in the parvocellular PVN, establishing a neural circuit-level inhibitory input to AVP gene expression within the HPA axis.

    Evidence Selective forebrain fiber tract lesions with in situ hybridization for AVP and CRH mRNA, plasma ACTH RIA in rats

    PMID:1333341

    Open questions at the time
    • neurotransmitter identity of the inhibitory hippocampal projection was unknown
    • single lesion study without chemogenetic or optogenetic confirmation
  5. 1993 Medium

    Intronic hnRNA measurements showed that emotional stress rapidly induces AVP gene transcription within 2 hours in the PVN, positioning transcriptional activation as the acute molecular response coupling psychological stress to HPA axis output.

    Evidence In situ hybridization with intron-specific riboprobe for AVP hnRNA in rat PVN after novel environment stress

    PMID:8317194

    Open questions at the time
    • upstream transcription factors driving stress-induced AVP transcription were not identified
    • single stressor paradigm
  6. 1993 High

    Nucleotide receptors (P2u) were found to oppose AVP-stimulated water permeability by activating PKC to suppress V2-coupled adenylate cyclase, revealing a paracrine brake on AVP antidiuresis in the inner medullary collecting duct.

    Evidence In vitro perfusion of terminal IMCD tubules with cAMP assay, PKC inhibitor calphostin C, cAMP analogue controls

    PMID:8594881

    Open questions at the time
    • physiological source and regulation of luminal ATP/UTP was not defined
    • whether P2u modulation operates in vivo was untested
  7. 1995 High

    Systematic pharmacological profiling identified V1b as the sole AVP receptor subtype mediating insulin secretion from pancreatic β-cells, extending V1b function beyond corticotropes to endocrine pancreas.

    Evidence Perfused rat pancreas and RINm5F cells with selective V1b, V1a, and OT receptor antagonists/agonists; insulin RIA

    PMID:8572202

    Open questions at the time
    • downstream intracellular signaling cascade from V1b to insulin granule exocytosis was not mapped
    • physiological contribution of AVP to glucose homeostasis in vivo was not quantified
  8. 1996 High

    PGE₂ was shown to reverse AVP-mediated inhibition of bicarbonate absorption in the MTAL through a PKC→Gᵢ→↓cAMP cascade, defining a complete counter-regulatory signaling pathway downstream of prostaglandin receptors that modulates AVP actions in the thick ascending limb.

    Evidence In vitro perfused MTAL segments with PKC inhibitors, PMA, pertussis toxin, and forskolin controls

    PMID:8764317

    Open questions at the time
    • specific EP receptor subtype responsible was not identified
    • whether this pathway operates during in vivo prostaglandin elevations (e.g. NSAID withdrawal) was untested
  9. 1997 High

    Mutagenesis of the Brattleboro AVP gene demonstrated that the neurophysin coding region is essential for precursor processing and secretion, establishing the molecular basis of autosomal recessive diabetes insipidus as a frameshift-induced protein-folding defect rather than simple loss of the glycopeptide.

    Evidence COS cell transfection with systematic stop-codon insertion constructs, AVP secretion by RIA

    PMID:9402088

    Open questions at the time
    • precise folding intermediate trapped by the frameshift-extended neurophysin was not structurally resolved
    • ER stress consequences of misfolded precursor were not examined
  10. 2001 Medium

    Demonstrating that corticosterone selectively gates norepinephrine-induced AVP (but not CRH) transcription in the PVN explained the differential regulation of the two HPA secretagogues and positioned glucocorticoid feedback as a preferential brake on AVP gene expression.

    Evidence Intra-PVN norepinephrine microinjection with intronic hnRNA ISH in adrenal-intact vs. adrenalectomized rats with corticosterone replacement

    PMID:11295232

    Open questions at the time
    • glucocorticoid response element mediating this selective suppression was not mapped
    • single neurotransmitter tested
  11. 2004 High

    In vivo tubule microperfusion identified that AVP stimulates distal K⁺ secretion through luminal V1 receptors via PLC/Ca²⁺/PKC activating BK (maxi-K) channels, rather than the canonical V2/cAMP/PKA pathway, establishing a novel effector pathway for AVP in potassium handling.

    Evidence In vivo stationary microperfusion of rat cortical distal tubules with K⁺-selective microelectrodes, H89, staurosporine, BAPTA, TEA, and iberiotoxin

    PMID:15253724

    Open questions at the time
    • molecular identity of the luminal V1 receptor subtype (V1a vs V1b) was not resolved
    • contribution to whole-body potassium balance was not quantified
  12. 2007 High

    CaSR activation attenuates AVP-induced AQP2 expression via calmodulin-dependent inhibition of cAMP accumulation, providing a molecular mechanism for hypercalcemia-associated nephrogenic diabetes insipidus.

    Evidence mpkCCDcl4 cells with CaSR agonists, CaSR siRNA, calmodulin inhibitor, cAMP and AQP2 protein/mRNA measurements

    PMID:18032798

    Open questions at the time
    • specific calmodulin target (e.g. AC isoform or PDE isoform) was not identified
    • in vivo confirmation in CaSR-deficient animals was not performed
  13. 2014 Medium

    Polycomb complex occupancy at the Avp downstream enhancer was shown to precede and prime early-life stress-responsive DNA methylation changes, establishing the epigenetic sequence (PcG → Tet binding → DNMT recruitment → MeCP2) that programs AVP gene regulation during development.

    Evidence ESC-derived hypothalamic-like differentiation model with ChIP for PcG/Tet/MeCP2/DNMT, bisulfite sequencing, and in vivo validation

    PMID:24599304

    Open questions at the time
    • whether this epigenetic sequence is causal for long-term AVP expression changes in vivo after ELS was not conclusively demonstrated
    • cell model may not fully recapitulate PVN neuron identity
  14. 2021 High

    Oestrogen was shown to suppress salt-dependent hypertension by reversing GABA excitation in magnocellular AVP neurons: DOCA-salt increased NKCC1 and decreased KCC2, shifting the Cl⁻ equilibrium to make GABA depolarizing; oestrogen restored normal Cl⁻ transporter expression and reduced plasma AVP and blood pressure.

    Evidence Whole-cell patch-clamp in identified AVP neurons in hypothalamic slices, NKCC1/KCC2 Western blot, plasma AVP RIA, blood pressure measurement, CLP290 rescue in DOCA-salt rats

    PMID:32960965

    Open questions at the time
    • oestrogen receptor subtype (ERα vs ERβ) and genomic vs non-genomic action on NKCC1/KCC2 were not dissected
    • whether this mechanism operates in human salt-sensitive hypertension is unknown
  15. 2021 Medium

    Activation of the apelin receptor was shown to oppose AVP antidiuresis by reducing V2-stimulated cAMP and AQP2 membrane insertion, demonstrating a druggable counter-regulatory axis relevant to hyponatremia correction.

    Evidence Collecting duct cell cAMP assay, AQP2 phosphorylation/trafficking by immunofluorescence, in vivo rat model of AVP-induced hyponatremia

    PMID:33436646

    Open questions at the time
    • molecular mechanism by which apelin receptor suppresses V2-coupled adenylate cyclase was not defined
    • single lab, not yet replicated in clinical hyponatremia
  16. 2022 High

    AVP was found to suppress macrophage antiviral IFN-I signaling by reducing AHI1, which normally recruits OTUD1 to deubiquitinate and stabilize Tyk2, thereby linking depression-associated AVP elevation to impaired innate immunity.

    Evidence Co-IP for AHI1–OTUD1–Tyk2, ubiquitination assays, AHI1 KD/overexpression, AVP treatment of macrophages, validated in MDD patient PBMCs and CUMS mouse model

    PMID:35821088

    Open questions at the time
    • AVP receptor subtype on macrophages mediating AHI1 downregulation was not identified
    • whether this pathway contributes to infection susceptibility in depression patients in vivo is unestablished

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of AVP precursor folding and its interaction with neurophysin during ER processing, the complete signaling architecture downstream of V1b in β-cells and corticotropes, and whether the AVP–AHI1–Tyk2 immunosuppressive axis is targetable for infection prevention in depression.
  • no high-resolution structure of the AVP-neurophysin precursor in the ER folding intermediate state
  • V1b downstream signaling to insulin exocytosis machinery not mapped
  • in vivo relevance of AVP-AHI1-Tyk2 axis to clinical infection susceptibility untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 6 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 7
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-382551 Transport of small molecules 5 R-HSA-168256 Immune System 1
Partners
AHI1AQP2AVPR1AAVPR1BAVPR2TYK2

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1984 AVP stimulates pituitary ACTH release through a receptor that is pharmacologically distinct from classical V1 (pressor) and V2 (antidiuretic) receptors. V1-antagonists only partially inhibited AVP-induced ACTH secretion, the V2 agonist dDAVP was 20–30-fold less potent than AVP, and oxytocin was only 4–8-fold less potent, together indicating AVP acts on corticotrope cells via a novel receptor subtype (later identified as V1b/V3). In vitro pharmacological antagonism assay using rat anterior pituitary gland segments with selective V1/V2 antagonists and agonists, measuring ACTH secretion by RIA Peptides High 6089144
1988 AVP induces rapid, concentration-dependent increases in intracellular Ca2+ ([Ca2+]i) and Ca2+ efflux in glomerular mesangial cells and causes cell contraction exclusively through V1 (pressor) receptors. This effect occurs partly via Ca2+ release from intracellular stores (even in Ca2+-free medium) and partly via Ca2+ influx; dantrolene (blocker of ER Ca2+ release) inhibited both Ca2+ efflux and contraction, whereas verapamil (Ca2+ channel blocker) only partially inhibited Ca2+ influx. Direct measurement of [Ca2+]i in adherent cultured mesangial cells, 45Ca2+ efflux assay, V1-selective antagonist d(CH2)5Tyr(Me)AVP, dantrolene and verapamil pharmacology, cell contraction assay The American journal of physiology High 3394807
1992 AVP and mineralocorticoids both stimulate Na+ transport in the cortical collecting duct by increasing the number and kinetic properties (open probability) of amiloride-sensitive Na+ channels in the apical membrane, but through distinct molecular mechanisms that allow synergism: AVP acts via cAMP/PKA to recruit quiescent channels and increase their open probability, while mineralocorticoids act via genomic pathways to synthesize new channels. Electrophysiological patch-clamp recording of apical Na+ channels combined with biochemical second-messenger studies in isolated perfused rat cortical collecting duct Kidney international High 1313121
1992 Hippocampal efferents travelling in the lateral fimbria-fornix tonically inhibit AVP mRNA expression in the medial parvocellular paraventricular nucleus (PVN). Lateral fimbria-fornix lesions, but not medial lesions or corticohypothalamic tract sections, increased both CRH mRNA and AVP mRNA in the PVN and elevated ACTH secretion, placing the hippocampal–lateral fornix–PVN AVP circuit as an inhibitory node in HPA axis regulation. Selective forebrain fiber tract lesions combined with semi-quantitative in situ hybridization histochemistry for CRH and AVP mRNA, and plasma ACTH RIA in rats Brain research Medium 1333341
1993 AVP-stimulated water permeability (Pf) in the inner medullary collecting duct is inhibited by extracellular nucleotides (ATP, UTP but not ADP) acting via P2u nucleotide receptors. This inhibition is upstream of cAMP: ATP decreased AVP-stimulated cAMP levels by ~32%, did not affect the Pf response to membrane-permeant cAMP analogues, and was abolished by the PKC inhibitor calphostin C, indicating the nucleotide receptor activates the phosphoinositide/PKC pathway to suppress adenylate cyclase coupling to the V2 receptor. In vitro perfusion of terminal IMCD tubules, osmotic water permeability measurements, cAMP assay in IMCD suspensions, PKC inhibitor calphostin C, cAMP analogue and forskolin controls The American journal of physiology High 8594881
1993 Epinephrine inhibits AVP-stimulated Na+ transport and osmotic water permeability in the cortical collecting duct via α2-adrenergic receptors. At low doses (100 nM) yohimbine (α2-antagonist) reversed the effect; epinephrine increased luminal membrane fractional resistance equivalently to amiloride, indicating blockade of apical amiloride-sensitive Na+ conductance. Residual (~40%) inhibition of cAMP-stimulated transport by epinephrine at high concentrations pointed to at least one additional intracellular messenger beyond adenylate cyclase inhibition. In vitro perfused cortical collecting ducts from Dahl-Rapp SS, SR and Sprague-Dawley rats; transepithelial voltage, Na+ flux, and water permeability measurements; 8-BrcAMP substitution; yohimbine pharmacology; amiloride comparison The American journal of physiology Medium 8105698
1993 Emotional stress rapidly increases AVP gene transcription (assessed by intronic heteronuclear RNA) in the paraventricular nucleus within 2 hours, preceding changes in cytoplasmic mRNA. This finding positioned transcriptional upregulation of the AVP gene as an acute molecular response mediating activation of the HPA axis during psychological stress. In situ hybridization with an intronic riboprobe (complementary to an AVP intron sequence) to detect AVP hnRNA as a surrogate for nascent gene transcription in rat PVN following novel environment stress Acta endocrinologica Medium 8317194
1995 AVP stimulates PGE2 synthesis in isolated rabbit cortical collecting tubules through a V1-type receptor pathway rather than V2/cAMP. dDAVP (a selective V2 agonist) elicited only a very weak response at high doses, whereas AVP produced an immediate, transient, dose-dependent stimulation (~150–200% above baseline) of PGE2 synthesis requiring exogenous arachidonic acid, indicating the PGE2 response is coupled to V1 receptor-linked phospholipase activation. Superfusion of microdissected rabbit cortical collecting tubules, enzyme immunoassay for PGE2, comparison of AVP vs. dDAVP dose-response The American journal of physiology Medium 2500029
1995 Expression cloning from rabbit renal medulla identified a novel AVP-activated, calcium-mobilizing receptor protein (VACM-1, 780 amino acids) that is distinct from V1 and V2 AVP receptors. When expressed in Xenopus oocytes or COS-1 cells, VACM-1 conferred high-affinity AVP binding (Kd ~2 nM) and AVP-induced intracellular Ca2+ mobilization; immunohistochemistry localized VACM-1 to collecting tubule epithelia. Expression cloning in Xenopus oocyte system, COS-1 cell transfection, 125I-AVP binding assay, Ca2+ mobilization assay, in vitro translation with immunoprecipitation, immunohistochemistry The American journal of physiology High 7611460
1995 Both AVP and oxytocin stimulate insulin release from the perfused rat pancreas and from RINm5F cells exclusively through V1b (V3) receptors, not V1a or oxytocin receptors. The selective V1b antagonist dP[Tyr(Me)2]AVP abolished insulin release by both peptides, the V1a antagonist was inactive, and the V1b agonist d[D-3-Pal]VP dose-dependently stimulated insulin release, defining V1b as the functional receptor on pancreatic β-cells. Perfused rat pancreas preparation, RINm5F cell insulin release assay, systematic pharmacological profiling with selective V1b, V1a, and oxytocin receptor antagonists and agonists; RIA for insulin The American journal of physiology High 8572202
1996 PGE2 reverses AVP-mediated inhibition of HCO3- absorption in the medullary thick ascending limb by activating protein kinase C (PKC), which in turn inhibits AVP-stimulated cAMP production via a Gi-dependent mechanism. PKC inhibitors (staurosporine, chelerythrine) blocked the PGE2 reversal, the PKC activator PMA mimicked PGE2, and pertussis toxin abolished the PMA effect, demonstrating PKC→Gi→↓cAMP as the signaling cascade. In vitro perfusion of rat MTAL segments, measurement of HCO3- absorption, PKC inhibitors staurosporine and chelerythrine, phorbol ester PMA, pertussis toxin pretreatment, comparison with forskolin The American journal of physiology High 8764317
1997 Both intact neurophysin (NP) coding region and the vasopressin (VP) coding region are required for proper AVP precursor processing and secretion. In COS cells transfected with Brattleboro (BB) rat AVP gene (which has a single guanine deletion in NP causing frameshift and loss of stop codon), no AVP was secreted; restoring a stop codon at the equivalent of the normal VP+NP length partially rescued secretion, whereas VP coding region alone was insufficient. This demonstrated that the BB frameshift in NP—not simply loss of glycopeptide coding region—is the molecular basis of diabetes insipidus in these rats. COS cell transfection with wild-type and mutated BB AVP gene constructs (systematic stop-codon insertion mutagenesis), AVP secretion measured by RIA, co-transfected β-galactosidase as internal control Journal of the American Society of Nephrology High 9402088
1997 AVP produced in suprachiasmatic nucleus (SCN) neurons tonically inhibits the CRH-adrenocorticotrope axis. Functional lesioning of SCN AVP neurons with AVP antibody–toxin conjugate decreased SCN AVP immunoreactive content and mRNA, increased CRH mRNA and decreased median eminence CRH immunoreactivity, and doubled plasma ACTH, positioning SCN-derived AVP as a direct upstream inhibitor of PVN CRH neurons. Targeted cytotoxic monoclonal antibody (anti-AVP) microinjection into rat SCN, AVP immunohistochemistry and RIA, AVP mRNA in situ hybridization, CRH mRNA ISH, CRH immunohistochemistry, plasma ACTH RIA Journal of neuroscience research Medium 9404718
1997 A dual angiotensin II/AVP receptor in the renal outer medullary thick ascending limb and inner medullary collecting duct responds equally to both Ang II and AVP; pharmacologically it behaves as a V2-type AVP receptor (displaced by DVDAVP) and a novel AT1-type angiotensin receptor coupled to adenylate cyclase (displaced by losartan but not PD 123319), distinct from prototype Ca2+-mobilizing AT1 receptors. Radioligand displacement binding assays with [3H]AVP and 125I-Ang II, selective V2 analogue DVDAVP, AT1 antagonist losartan, AT2 antagonist PD 123319, immunocytochemistry of renal sections Hypertension Medium 9095083
2001 Norepinephrine microinjected into the rat PVN differentially regulates CRH and AVP gene transcription: it strongly increases CRH hnRNA but does not affect AVP hnRNA in adrenal-intact animals. Removing the corticosterone feedback (adrenalectomy with basal corticosterone replacement) unmasked a significant NE-induced increase in AVP hnRNA, demonstrating that corticosterone exerts greater suppressive control over AVP gene transcription than over CRH, thereby explaining differential secretagogue regulation of the HPA axis. Intra-PVN norepinephrine microinjection in conscious rats, semi-quantitative in situ hybridization with intron-specific riboprobes for CRH and AVP hnRNA, adrenalectomy with subcutaneous corticosterone pellet model Brain research. Molecular brain research Medium 11295232
2004 AVP stimulates distal tubular K+ secretion via luminal V1 receptors through a PLC/Ca2+/PKC signaling pathway, not through adenylate cyclase/cAMP/PKA. In vivo microperfusion showed that PKC inhibitor staurosporine (45% inhibition) and the Ca2+ chelator BAPTA (41% inhibition) blocked AVP-stimulated K+ flux, while the PKA inhibitor H89 had no effect; AVP-stimulated K+ secretion was further reduced by BK (maxi-K) channel blockers TEA and iberiotoxin, identifying the downstream effector channel. In vivo stationary microperfusion of rat cortical distal tubules, double-barreled K+-selective microelectrodes, selective inhibitors for PKA (H89), PKC (staurosporine), Ca2+ chelation (BAPTA), and BK channel blockers (TEA, iberiotoxin) Kidney international High 15253724
2005 Repeated agonistic encounters (dominant experience) selectively increase AVP V1a receptor binding in the lateral ventromedial hypothalamus (VMHL) of dominant hamsters compared to subordinates, independent of testosterone levels. Acute social defeat alone does not alter V1a receptor binding, indicating that experience-dependent plasticity in V1a receptor density in a specific hypothalamic nucleus correlates with and may mediate the behavioral changes associated with repeated social victory. Radioligand receptor autoradiography with [125I]linear AVP across multiple brain regions, plasma testosterone RIA, controlled dominant/subordinate agonistic encounter paradigm in Syrian hamsters Hormones and behavior Medium 15935353
2007 The calcium-sensing receptor (CaSR) attenuates AVP-induced aquaporin-2 (AQP2) expression in cortical collecting duct principal cells via a calmodulin-dependent mechanism. High extracellular Ca2+ or CaSR agonists (neomycin, Gd3+) reduced AVP-induced cAMP accumulation and AQP2 mRNA/protein; this was not due to phosphodiesterase activation or direct adenylate cyclase inhibition, but was prevented by calmodulin inhibition; CaSR gene silencing abolished the effect. Mouse cortical collecting duct cell line (mpkCCDcl4), CaSR agonist pharmacology, CaSR gene silencing (siRNA), cAMP measurement, AQP2 mRNA and protein quantification, phosphodiesterase and adenylate cyclase pharmacological dissection, calmodulin inhibitor Journal of the American Society of Nephrology High 18032798
2014 Polycomb group (PcG) complex binding at the Avp downstream enhancer precedes and primes the emergence of early-life stress (ELS)-responsive DNA methylation at that locus. In an embryonic stem cell-derived hypothalamic-like differentiation model, PcG occupancy correlated with gene silencing and co-occurred with Tet protein binding (preventing premature DNA methylation); differentiation evicted PcG complexes, leading to DNMT recruitment and enhancer methylation, then increased MeCP2 binding—establishing the epigenetic sequence controlling Avp enhancer programming. ESC-derived hypothalamic-like differentiation model, chromatin immunoprecipitation (ChIP) for PcG proteins (EZH2, SUZ12), Tet1/Tet2, MeCP2, DNMT3a/b; bisulfite sequencing for DNA methylation; in vivo mouse experiments; Avp mRNA quantification PloS one Medium 24599304
2021 Activating the apelin receptor (apelin-R) with a metabolically stable apelin-17 analog (LIT01-196) opposes AVP-mediated antidiuresis by decreasing dDAVP-induced cAMP production and reducing apical cell-surface expression of phosphorylated aquaporin-2 in collecting duct cells via V2 receptor modulation, thereby increasing aqueous diuresis and correcting experimental hyponatremia. In vivo rat pharmacokinetics (subcutaneous administration), collecting duct cell cAMP assay, AQP2 phosphorylation and membrane trafficking by immunofluorescence, rat model of AVP-induced hyponatremia with urinary osmolality and serum sodium measurements Nature communications Medium 33436646
2021 Oestrogen inhibits salt-dependent hypertension by suppressing GABAergic excitation in hypothalamic magnocellular AVP neurons. DOCA-salt treatment converted GABAergic inhibition to excitation in AVP neurons (due to increased NKCC1/decreased KCC2 expression shifting the chloride equilibrium potential), raised plasma AVP and blood pressure; oestrogen reversed all these effects by modulating NKCC1 and KCC2 activity/expression, and the KCC2 activator CLP290 phenocopied oestrogen. Rat DOCA-salt uninephrectomy hypertension model, whole-cell patch-clamp electrophysiology of AVP neurons in hypothalamic slices, GABA equilibrium potential measurement, plasma AVP RIA, blood pressure measurement, Western blotting for NKCC1/KCC2, in vivo CLP290 treatment Cardiovascular research High 32960965
2022 Depression-associated elevations in AVP reduce AHI1 expression in macrophages, thereby impairing type-I interferon (IFN-I) antiviral signaling. Mechanistically, AHI1 recruits the deubiquitinase OTUD1 to stabilize Tyk2; AVP-driven AHI1 reduction leads to Tyk2 destabilization and attenuated IFN-I signaling. This identifies an AVP→AHI1→OTUD1→Tyk2→IFN-I axis connecting depression-related neuropeptide signaling to innate antiviral immunity. PBMCs and macrophages from MDD patients, depression model mice (CUMS), AHI1 knockdown/overexpression, Co-IP to demonstrate AHI1–OTUD1–Tyk2 interaction, ubiquitination assays, IFN-I signaling readouts (STAT1 phosphorylation), AVP treatment of macrophages, meptazinol pharmacology Cell research High 35821088

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 A role for mitochondria in NLRP3 inflammasome activation. Nature 4626 21124315
2006 Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 4145 16407889
2009 Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. Journal of immunology (Baltimore, Md. : 1950) 2467 19570822
2008 Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nature immunology 2415 18604214
2015 A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nature medicine 2295 25686105
2012 NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 2289 23254930
2016 Mechanism and Regulation of NLRP3 Inflammasome Activation. Trends in biochemical sciences 2273 27669650
2011 The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nature medicine 2134 21217695
2009 AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 2117 19158675
2008 Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science (New York, N.Y.) 2104 18403674
2015 Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion. Cell research 2071 26611636
2012 Inflammasomes in health and disease. Nature 1834 22258606
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2004 NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity 1452 15030775
2001 Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nature genetics 1304 11687797
2007 Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell death and differentiation 1169 17599094
2014 Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Cell 1140 24630722
2016 NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux. Nature 1063 26814970
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2015 Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome. Cell 849 25594175
2019 MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition. Nature chemical biology 812 31086327
2010 Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation. PloS one 797 20668705
2003 NODs: intracellular proteins involved in inflammation and apoptosis. Nature reviews. Immunology 776 12766759
2013 Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation. Immunity 771 23954133
2009 Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. The Journal of cell biology 699 19805629
2021 Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients. The Journal of experimental medicine 657 33231615
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2019 Structural mechanism for NEK7-licensed activation of NLRP3 inflammasome. Nature 644 31189953
2012 Novel role of PKR in inflammasome activation and HMGB1 release. Nature 639 22801494
2012 Non-transcriptional priming and deubiquitination regulate NLRP3 inflammasome activation. The Journal of biological chemistry 635 22948162
1999 Colinearity and its exceptions in orthologous adh regions of maize and sorghum. Proceedings of the National Academy of Sciences of the United States of America 207 10377428
1994 Differential interactions of promoter elements in stress responses of the Arabidopsis Adh gene. Plant physiology 189 7972489
1992 Regulation of Na+ channels in the cortical collecting duct by AVP and mineralocorticoids. Kidney international 136 1313121
2008 Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the cancer diseases. Clinica chimica acta; international journal of clinical chemistry 132 18505683
1992 Selective forebrain fiber tract lesions implicate ventral hippocampal structures in tonic regulation of paraventricular nucleus corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) mRNA expression. Brain research 116 1333341
1995 TAFs and TFIIA mediate differential utilization of the tandem Adh promoters. Cell 102 7664336
1995 Extracellular nucleotide receptor inhibits AVP-stimulated water permeability in inner medullary collecting duct. The American journal of physiology 95 8594881
2011 The plant ADH gene family. The Plant journal : for cell and molecular biology 94 21443628
1984 Evidence that the effects of arginine-8-vasopressin (AVP) on pituitary corticotropin (ACTH) release are mediated by a novel type of receptor. Peptides 90 6089144
2013 Extended genetic effects of ADH cluster genes on the risk of alcohol dependence: from GWAS to replication. Human genetics 84 23456092
2007 Calcium-sensing receptor attenuates AVP-induced aquaporin-2 expression via a calmodulin-dependent mechanism. Journal of the American Society of Nephrology : JASN 75 18032798
1977 Genetic and cytogenetic analysis of the Adh region in Drosophila melanogaster. Genetics 70 408228
1994 Purification of acetaldehyde dehydrogenase and alcohol dehydrogenases from Thermoanaerobacter ethanolicus 39E and characterization of the secondary-alcohol dehydrogenase (2 degrees Adh) as a bifunctional alcohol dehydrogenase--acetyl-CoA reductive thioesterase. The Biochemical journal 69 8068002
1983 Characterization of 3H-AVP binding sites in particulate preparations of rat brain. Peptides 68 6415623
2021 Roles of Neuropeptides, VIP and AVP, in the Mammalian Central Circadian Clock. Frontiers in neuroscience 67 33935635
1996 Transcription factor veracity: is GBF3 responsible for ABA-regulated expression of Arabidopsis Adh? The Plant cell 67 8672884
1985 Mutation of the Adh gene of Drosophila melanogaster containing an internal tandem duplication. Journal of molecular biology 61 2419573
1995 Expression cloning of an AVP-activated, calcium-mobilizing receptor from rabbit kidney medulla. The American journal of physiology 57 7611460
1995 Effect of AVP and oxytocin on insulin release: involvement of V1b receptors. The American journal of physiology 55 8572202
1989 Characterization of the temperate bacteriophage phi adh and plasmid transduction in Lactobacillus acidophilus ADH. Applied and environmental microbiology 52 2508554
2001 Identification and cloning of gusA, encoding a new beta-glucuronidase from Lactobacillus gasseri ADH. Applied and environmental microbiology 51 11229918
2005 Ethanol rapidly causes activation of JNK associated with ER stress under inhibition of ADH. FEBS letters 50 16343492
2015 Calcilytic Ameliorates Abnormalities of Mutant Calcium-Sensing Receptor (CaSR) Knock-In Mice Mimicking Autosomal Dominant Hypocalcemia (ADH). Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 49 25967373
2005 Repeated agonistic encounters in hamsters modulate AVP V1a receptor binding. Hormones and behavior 49 15935353
1990 Characterization of the Arabidopsis Adh G-box binding factor. The Plant cell 47 2152176
1988 AVP-induced Ca fluxes and contraction of rat glomerular mesangial cells. The American journal of physiology 47 3394807
1993 ADH and ALDH genotype profiles in Caucasians with alcohol-related problems and controls. Addiction (Abingdon, England) 46 8461855
2022 Depression compromises antiviral innate immunity via the AVP-AHI1-Tyk2 axis. Cell research 43 35821088
2019 Alcohol Intake Interacts with Functional Genetic Polymorphisms of Aldehyde Dehydrogenase (ALDH2) and Alcohol Dehydrogenase (ADH) to Increase Esophageal Squamous Cell Cancer Risk. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 43 30639619
1998 Intra- and interspecific DNA variation and codon bias of the alcohol dehydrogenase (Adh) locus in Arabis and Arabidopsis species. Molecular biology and evolution 43 12572606
1980 Aldosterone and ADH response to heat and dehydration in cattle. Journal of applied physiology: respiratory, environmental and exercise physiology 43 7364609
1982 Genetic variation in the expression of ADH in Drosophila melanogaster. Genetics 42 6816669
1984 Nucleotide sequence comparison of the Adh gene in three drosophilids. Journal of molecular evolution 41 6429340
2003 Sequence variation of alcohol dehydrogenase (Adh) paralogs in cactophilic Drosophila. Genetics 39 12586706
1993 Molecular variation of Adh and P6 genes in an African population of Drosophila melanogaster and its relation to chromosomal inversions. Genetics 39 8349110
1988 Quantitative analysis of RNA produced by slow and fast alleles of Adh in Drosophila melanogaster. Proceedings of the National Academy of Sciences of the United States of America 39 2455893
2020 Sex-dependent effects of social status on the regulation of arginine-vasopressin (AVP) V1a, oxytocin (OT), and serotonin (5-HT) 1A receptor binding and aggression in Syrian hamsters (Mesocricetus auratus). Hormones and behavior 38 33148500
1975 Actions of external hypertonic urea, ADH, and theophylline on transcellular and extracellular solute permeabilities in frog skin. The Journal of general physiology 38 1080796
1990 Conserved enhancer and silencer elements responsible for differential Adh transcription in Drosophila cell lines. Molecular and cellular biology 37 1694013
1999 No association between DRD2 locus and alcoholism after controlling the ADH and ALDH genotypes in Chinese Han population. Alcoholism, clinical and experimental research 36 10235293
1983 Biochemical and molecular analysis of naturally occurring Adh variants in Drosophila melanogaster. Proceedings of the National Academy of Sciences of the United States of America 35 6410397
1993 Inhibition by epinephrine of AVP- and cAMP-stimulated Na+ and water transport in Dahl rat CCD. The American journal of physiology 34 8105698
1993 In situ hybridization of arginine vasopressin (AVP) heteronuclear ribonucleic acid reveals increased AVP gene transcription in the rat hypothalamic paraventricular nucleus in response to emotional stress. Acta endocrinologica 34 8317194
1989 Neuropeptide Y (NPY) and vasopressin (AVP) in the hypothalamo-neurohypophysial axis of salt-loaded or Brattleboro rats. Brain research 34 2731031
1988 Structure and evolution of the Adh genes of Drosophila mojavensis. Genetics 34 3224808
2006 AVP receptor antagonists as aquaretics: review and assessment of clinical data. Cleveland Clinic journal of medicine 33 16970150
2003 Effect of indomethacin on the c-fos expression in AVP and TH neurons in rat brain induced by lipopolysaccharide. Brain research 32 12646303
2003 Population genetics and geographic variation of alcohol dehydrogenase (Adh) paralogs and glucose-6-phosphate dehydrogenase (G6pd) in Drosophila mojavensis. Molecular biology and evolution 31 14660699
2001 Norepinephrine-induced CRH and AVP gene transcription within the hypothalamus: differential regulation by corticosterone. Brain research. Molecular brain research 31 11295232
1983 Genetic control of Adh expression in Drosophila melanogaster. Genetics 31 6416923
2008 Alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) activity in the sera of patients with gastric cancer. Digestive diseases and sciences 30 18231859
2008 Alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) activity in the sera of patients with liver cancer. Journal of clinical laboratory analysis 30 18484658
2014 Polycomb binding precedes early-life stress responsive DNA methylation at the Avp enhancer. PloS one 29 24599304
2012 Nicotine stimulates secretion of corticosterone via both CRH and AVP receptors. Journal of neurochemistry 29 22191943
1996 PGE2 reverses AVP inhibition of HCO3- absorption in rat MTAL by activation of protein kinase C. The American journal of physiology 29 8764317
2007 Acetaldehyde and alcoholic cardiomyopathy: lessons from the ADH and ALDH2 transgenic models. Novartis Foundation symposium 28 17590987
2004 Human variability for metabolic pathways with limited data (CYP2A6, CYP2C9, CYP2E1, ADH, esterases, glycine and sulphate conjugation). Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 28 14871582
2000 Phylogeny, duplication, and intraspecific variation of Adh sequences in New World diploid cottons (Gossypium l., malvaceae). Molecular phylogenetics and evolution 28 10877941
1999 Transcriptional control of ADH genes in the xylose-fermenting yeast Pichia stipitis. Applied and environmental microbiology 28 10347014
1991 Characterization of the structure and evolution of the Adh region of Drosophila hydei. Genetics 28 2004708
2021 A metabolically stable apelin-17 analog decreases AVP-induced antidiuresis and improves hyponatremia. Nature communications 27 33436646
2019 Limitations of the Avp-IRES2-Cre (JAX #023530) and Vip-IRES-Cre (JAX #010908) Models for Chronobiological Investigations. Journal of biological rhythms 26 31452438
1997 Arginine vasopressin (AVP) depletion in neurons of the suprachiasmatic nuclei affects the AVP content of the paraventricular neurons and stimulates adrenocorticotrophic hormone release. Journal of neuroscience research 26 9404718
2019 The Characteristics and Genome Analysis of vB_AviM_AVP, the First Phage Infecting Aerococcus viridans. Viruses 24 30691182
2008 The activity of class I, II, III, and IV alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) in esophageal cancer. Digestive diseases and sciences 24 18688716
1987 AVP-induced pulmonary vasodilation during specific V1 receptor block in conscious dogs. The American journal of physiology 24 2888317
1987 Absence of significant cellular dilution during ADH-stimulated water reabsorption. Science (New York, N.Y.) 24 3823867
2001 Increased synthesis and avp unresponsiveness of Na,K-ATPase in collecting duct from nephrotic rats. Journal of the American Society of Nephrology : JASN 23 11675400
1991 [3H]desGly-NH2(9)-d(CH2)5[D-Ileu2,Ileu4]AVP: an AVP V2 receptor antagonist radioligand. Peptides 23 1815207
1989 Molecular analysis of an alcohol dehydrogenase (Adh) gene from chromosome 1 of wheat. Genome 23 2545522
2017 Improving Acetic Acid Production by Over-Expressing PQQ-ADH in Acetobacter pasteurianus. Frontiers in microbiology 22 28932219
1989 Latitudinal variation of Adh gene frequencies in Drosophila melanogaster: a Mediterranean instability. Heredity 22 2499559
2014 Molecular variation in AVP and AVPR1a in New World monkeys (Primates, Platyrrhini): evolution and implications for social monogamy. PloS one 21 25360668
2007 Variations in ADH and ALDH in Southwest California Indians. Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism 21 17718395
1983 Control of Na+ and water absorption across vertebrate "tight epithelia by adh and aldosterone. The Journal of experimental biology 21 6317791
2008 Alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) activity in the sera of patients with colorectal cancer. Clinical and experimental medicine 20 18188528
1997 Renal immunocytochemical distribution and pharmacological properties of the dual angiotensin II/AVP receptor. Hypertension (Dallas, Tex. : 1979) 20 9095083
1996 The role of brain angiotensin in thirst and AVP release induced by hemorrhage. Regulatory peptides 20 8899885
1990 Sequence analysis of two null-mutant alleles of the single Arabidopsis Adh locus. Molecular & general genetics : MGG 20 2277648
1989 Effects of AVP and dDAVP on PGE2 synthesis in superfused cortical collecting tubules. The American journal of physiology 20 2500029
2022 AvP: A software package for automatic phylogenetic detection of candidate horizontal gene transfers. PLoS computational biology 19 36350852
2000 Evolution of a glucose-regulated ADH gene in the genus Saccharomyces. Gene 19 10717481
1993 Characterization and evolution of the Adh genomic region in Drosophila guanche and Drosophila madeirensis. Molecular phylogenetics and evolution 19 8081544
2012 Mutations in the AVPR2, AVP-NPII, and AQP2 genes in Turkish patients with diabetes insipidus. Endocrine 18 22644838
2006 Arabidopsis thaliana expresses two functional isoforms of Arvp, a protein involved in the regulation of cellular lipid homeostasis. Biochimica et biophysica acta 18 16725371
2006 Cardiac overexpression of alcohol dehydrogenase (ADH) alleviates aging-associated cardiomyocyte contractile dysfunction: role of intracellular Ca2+ cycling proteins. Aging cell 18 16842498
1997 Arginine vasopressin secretion with mutants of wild-type and Brattleboro rats AVP gene. Journal of the American Society of Nephrology : JASN 18 9402088
1989 Analysis of Adh gene regulation in Drosophila: studies using somatic transformation. Developmental genetics 18 2500285
2015 Functional analysis of alcohol dehydrogenase (ADH) genes in Pichia pastoris. Biotechnology letters 17 26573637
2005 Autosomal dominant neurohypophyseal diabetes insipidus with linkage to chromosome 20p13 but without mutations in the AVP-NPII gene. The Journal of clinical endocrinology and metabolism 17 15811933
2005 TGFalpha and AVP in the mouse suprachiasmatic nucleus: anatomical relationship and daily profiles. Brain research 17 16051199
2004 Signaling path of the action of AVP on distal K+ secretion. Kidney international 17 15253724
2003 Alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) activity in the human pancreas. Digestive diseases and sciences 17 12870777
2011 Dose-Dependent Change in Elimination Kinetics of Ethanol due to Shift of Dominant Metabolizing Enzyme from ADH 1 (Class I) to ADH 3 (Class III) in Mouse. International journal of hepatology 16 22164338
1997 Modulation of genetic hypertension by short-term AVP V1A or V2 receptor antagonism in young SHR. The American journal of physiology 16 9124400
2021 Oestrogen inhibits salt-dependent hypertension by suppressing GABAergic excitation in magnocellular AVP neurons. Cardiovascular research 15 32960965
2012 Effects of Chronic Central Arginine Vasopressin (AVP) on Maternal Behavior in Chronically Stressed Rat Dams. Brain sciences 15 24349762
2011 Molecular evolution of Adh and LEAFY and the phylogenetic utility of their introns in Pyrus (Rosaceae). BMC evolutionary biology 15 21917170
2010 Associations between ADH gene variants and alcohol phenotypes in Dutch adults. Twin research and human genetics : the official journal of the International Society for Twin Studies 15 20158305
1995 The Arabidopsis Adh gene exhibits diverse nucleosome arrangements within a small DNase I-sensitive domain. The Plant cell 15 8535143