Arginine vasopressin receptor 1A
|Symbols||; AVPR V1a; AVPR1; V1aR|
|External IDs||IUPHAR: ChEMBL: GeneCards:|
|RNA expression pattern|
|File:PBB GE AVPR1A 206251 s at tn.png|
|File:PBB GE AVPR1A 206250 x at tn.png|
|File:PBB GE AVPR1A 206252 s at tn.png|
Arginine vasopressin receptor 1A (officially called AVPR1A) is one of the three major receptor types for arginine vasopressin (AVPR1B and AVPR2 being the others), and is present throughout the brain, as well as in the periphery in the liver, kidney, and vasculature.
Arginine vasopressin receptor 1A is also known as:
- V1a vasopressin receptor
- antidiuretic hormone receptor 1A
- SCCL vasopressin subtype 1a receptor
- V1-vascular vasopressin receptor AVPR1A
- vascular/hepatic-type arginine vasopressin receptor
Structure and function
Human AVPR1A cDNA is 1472 bp long and encodes a 418 amino-acid long polypeptide which shares 72%, 36%, 37%, and 45% sequence identity with rat Avpr1a, human AVPR2, rat Avpr2, and human oxytocin receptor (OXTR), respectively. AVPR1A is a G-protein coupled receptor (GPCR) with 7 transmembrane domains that couples to Gaq/11 GTP binding proteins, which along with Gbl, activate phospholipase C activity. Clinically, the V1A receptor is related to vasoconstriction compared to the V1B receptor that is more related to ACTH release or the V2 receptor that is linked to the diuretic function of ADH.
In the N-terminal juxtamembrane segment of the AVPR1A, the glutamate residue at position 54 (E54) and the arginine residue at position 46 (R46) are critical for binding with AVP and AVP agonists, with E54 likely to interact with AVP and R46 to contribute to a conformational switch.
Competitors of [125I]Tyr-Phaa-specific binding to AVPR1A include:
- Linear V1a antagonist phenylacetyl-D-Tyr(Et)-Phe-Gln-Asn-Lys-Pro-Arg-NH2 (Ki = 1.2 ± 0.2 nM)
- Relcovaptan (SR-49059) (Ki = 1.3 ± 0.2 nM)
- AVP (Ki = 1.8 ± 0.4 nM)
- Linear V1a antagonist phenylacetyl-D-Tyr(Et)-Phe-Val-Asn-Lys-Pro-Tyr-NH2 (Ki = 3.0 ± 0.5 nM)
- V2 antagonist d(CH2)5-[D-Ile2, Ile4, Ala-NH2]AVP (Ki = 68 ± 17 nM)
- Oxytocin (Ki = 129 ± 22 nM)
The AVPR1A is endocytosed by binding to beta arrestin, which dissociates rapidly from AVPR1A to allow it to return to the plasma membrane; however, upon activation, AVPR1A can heterodimerize with AVPR2 to increase beta-arrestin-mediated endocytosis (and intracellular accumulation) of AVPR1A, since AVPR2 is far less likely to dissociate from beta-arrestin.
Role in behavior
Prairie vs. montane voles
Males treated with OXT showed increases in Avpr1a in the ventral palladium, lateral septum, and cingulate cortex, while females showed decreases; males treated with an OTA showed decreases in AVPR1A in the bed nucleus of the stria terminalis, medial preoptic area of the hypothalamus, and lateral septum.
Although the Avpr1a coding region is 99% identical between prairie and montane voles, and binding and second messenger activity does not differ, patterns of distribution of Avpr1a differ drastically.
Male knockout mice in Avpr1a have reduced anxiety-like behavior and greatly impaired social recognition abilities, without any defects in spatial and nonsocial olfactory learning and memory tasks, as measured by the elevated plus maze, light/dark box, Morris water maze, forced swim, baseline acoustic startle and prepulse inhibition (PPI), and olfactory habituation tests. Some studies have shown Avpr1a knockout mice to have deficits in their circadian rhythms and olfaction.
Avpr1a’s role in social recognition is particularly important in the lateral septum, as using viral vectors to replace inactivated Avpr1a expression rescues social recognition and increases anxiety-related behavior. However, conflicting results have been found in another study. Also, unlike vasopressin 1b receptor and oxytcoin knockout mice, Avpr1a KO mice have a normal Bruce effect (appropriate failure of pregnancy in presence of novel male).
Avpr1a transcripts are diurnally expressed 12 hours out of phase from vasopressin expression in vasopressin and vasoactive intestinal polypeptide neurons of the suprachiasmatic nucleus in both vasopressin-normal Sprague-Dawley rats, as well as vasopressin-deficient Brattleboro rats.
Rats with reduced Avpr1a in the bed nucleus of the stria terminalis have increased incidences of the isolation potentiated startle, a measure of isolation-induced anxiety.
Interestingly, subchronic phencyclidine (PCP) treatment (which induces schizophrenic symptoms) reduces Avpr1a density in many brain regions, implying there might be a role for AVPR1A in schizophrenia.
Avpr1a is present in the lateral septum, neocortical layer IV, hippocampal formation, amygdalostriatal area, bed nucleus of the stria terminalis, suprachiasmatic nucleus, ventral tegmental area, substantia nigra, superior colliculus, dorsal raphe, nucleus of the solitary tract, spinal cord, and inferior olive, while mRNA transcripts for Avpr1a are found in the olfactory bulb, hippocampal formation, lateral septum, suprachiasmatic nucleus, paraventricular nucleus, anterior hypothalamic area, arcuate nucleus, lateral habenula, ventral tegmental area, substantia nigra (pars compacta), superior colliculus, raphe nuclei, locus coeruleus, inferior olive, choroid plexus, endothelial cells, area postrema and nucleus of the solitary tract.
Although vasopressin cell and fibre distribution patterns are highly conserved across species (with centrally projecting systems being sexually dimorphic), the vasopressin receptor AVPR1A distribution differs both between and within species; vasopressin production occurs in the hypothalamus, bed nucleus of the stria terminalis, and the medial amygdala (projecting to the lateral septum and ventral pallidum), while vasopressin binding sites in humans are in the lateral septum, thalamus, basal amygdaloid nucleus, and brainstem, but not cortex.
Human AVPR1A is situated on chromosome 12q14-15, and the promoter region does not have repeat sequences homologous to those found in prairie voles. Three polymorphic repetitive sequences have been found in humans in the 5’ flanking region: RS3, RS1, and a (GT)25 dinucleotide repeat.
The AVPR1A repeat polymorphism RS3 is a complex (CT)4-TT-(CT)8-(GT)24 repeat that is 3625 bp upstream of the transcription start site.
Homozygosity in allele 334 of RS3 is associated in men (but not women) with problems with pair-bonding behavior, measured by traits such as partner bonding, perceived marital problems, marital status, as well as spousal perception of marital quality.
In a study of 203 male and female university students, participants with short (308-325 bp) vs. long (327-342) versions of RS3 were less generous, as measured by lower scores on both money allocations in the dictator game, as well as by self-report with the Bardi-Schwartz Universalism and Benevolence Value-expressive Behavior Scales; although the precise functional significance of longer AVPR1A RS3 repeats is not known, they are associated with higher AVPR1A postmortem hippocampal mRNA levels.
Relative to all other alleles, the 334 allele of RS3 shows overactivation of left amygdala (in response to fearful face stimuli), with longer variants of RS3 additionally associated with stronger amygdala activation.
The AVPR1A repeat polymorphism RS1 is a (GATA)14 tetranucleotide repeat that is 553 bp upstream from the transcription start site. Allele 320 in RS1 is associated with increased novelty seeking and decreased harm avoidance; additionally, relative to all other alleles, the 320 allele of RS1 showed significantly less activity in the left amygdala, with shorter variants showing a trend of stronger activity.
The AGAT polymorphism is associated with age of first intercourse in females, with those homozygous for long repeats more likely to have sex before age 15 than any other genotype. However, there is no evidence of preferential transmission of AVPR1A microsatellite repeats to hypersexual or uninhibited people-seeking.
Polymorphisms in AVPR1A have also been shown to be associated with social interaction skills, and have been linked to such diverse traits as dancing and musical ability, altruism and autism.
Chimpanzees populations have individuals with single (only (GT)25 microsatellite) and duplicated (the (GT)25 microsatellite as well as the RS3) alleles, with allele frequencies of 0.795 and 0.205, respectively.
- Caldwell HK, Lee HJ, Macbeth AH, Young WS (2008). "Vasopressin: behavioral roles of an ‘original’ neuropeptide". Prog Neurobiol 84 (1): 1–24. PMC 2292122. PMID 18053631. doi:10.1016/j.pneurobio.2007.10.007.
- Thibonnier M, Auzan C, Madhun Z, Wilkins P, Berti-Mattera L, Clauser E (1994). "Molecular cloning, sequencing, and functional expression of a cDNA encoding the human V1a vasopressin receptor". J Biol Chem. 269 (5): 3304–10. PMID 8106369.
- Hawtin SR, Wesley VJ, Simms J, Argent CCH, Latif K, Wheatley (2005). "The N-terminal juxtamembrane segment of the V1a vasopressin receptor provides two independent epitopes required for high-affinity agonist binding and signaling.". Mol. Endocrinology 19 (11): 2871–2881. PMID 15994199. doi:10.1210/me.2005-0148.
- Terrillon S, Barberis C, Bouvier M (2004). "Heterodimerization of V1a and V2 vasopressin receptors determines the interaction with beta-arrestin and their trafficking patterns". PNAS 101 (6): 1548–53. PMC 341772. PMID 14757828. doi:10.1073/pnas.0305322101.
- Knafo A, Israel S, Darvasi A, Bachner-Melman R, Uzefovsky F, Cohen L, Feldman E, Lerer E, Laiba E, Raz Y, Nemanov L, Gritsenko I, Dina C, Agam G, Dean B, Bornstein G, Ebstein RP (2007). "Individual differences in allocation of funds in the dictator game associated with length of the arginine vasopressin 1a receptor RS3 promoter region and correlation between RS3 length and hippocampal mRNA". Genes, Brain and Behavior 7 (3): 266–75. PMID 17696996. doi:10.1111/j.1601-183X.2007.00341.x.
- Hopkin, Michael (April 2008). "'Ruthlessness gene' discovered". Nature@News. doi:10.1038/news.2008.738.
Dictatorial behaviour may be partly genetic, study suggests
- Bales KL, Plotsky PM, Young LJ, Lim MM, Grotte N, Ferrer E, Carter CS (2007). "Neonatal oxytocin manipulations have long-lasting sexually dimorphic effects on vasopressin receptors". Neuroscience 144 (1): 38–45. PMC 1774559. PMID 17055176. doi:10.1016/j.neuroscience.2006.09.009.
- Nair HP, Young LJ (2006). "Vasopressin and pair-bond formation: genes to brain to behavior". Physiology 21 (2): 146–152. PMID 16565480. doi:10.1152/physiol.00049.2005.
- Bielsky IF, Hu SB, Szegda KL, Westphal H, Young LJ (2004). "Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice". Neuropsychopharmacology 29 (3): 483–93. PMID 14647484. doi:10.1038/sj.npp.1300360.
- Wersinger SR, Caldwell HK, Martinez L, Gold P, Hu SB, Young WS (2007). "Vasopressin 1a receptor knockout mice have a subtle olfactory deficit but normal aggression". Physiology 6 (6): 540–51. PMID 17083331. doi:10.1111/j.1601-183X.2006.00281.x.
- Li JD, Burton KJ, Zhang C, Hu SB, Zhou QY. (Mar 2009). "Vasopressin receptor V1a regulates circadian rhythms of locomotor activity and expression of clock-controlled genes in the suprachiasmatic nuclei.". Am J Physiol Regul Integr Comp Physiol. 296 (3): R824–30. doi:10.1152/ajpregu.90463.2008.
- Bielsky IF, Hu SB, Ren X, Terwilliger EF, Young LJ (2005). "The V1a vasopressin receptor is necessary and sufficient for normal social recognition: a gene replacement study". Neuron 47 (4): 503–13. PMID 16102534. doi:10.1016/j.neuron.2005.06.031.
- Wersinger SR, Temple JL, Caldwell HK, Young WS 3rd. (Jan 2008). "Inactivation of the oxytocin and the vasopressin (Avp) 1b receptor genes, but not the Avp 1a receptor gene, differentially impairs the Bruce effect in laboratory mice (Mus musculus).". Endocrinology 149 (1): 116–21. PMC 2194605. PMID 17947352. doi:10.1210/en.2007-1056.
- Bielsky IF, Hu SB, Young LJ (2005). "Sexual dimorphism in the vasopressin system: lack of an altered behavioral phenotype in female V1aR knockout mice". Behav. Brain Res. 164 (1): 132–6. PMID 16046007. doi:10.1016/j.bbr.2005.06.005.
- Young WS, Kovacs K, Lolait SJ (1993). "The diurnal rhythm in vasopressin V1a receptor expression in the suprachiasmatic nucleus is not dependent on vasopressin". Endocrinology 133 (2): 585–90. PMID 8344200. doi:10.1210/en.133.2.585.
- Nair HP, Gutman AR, Davis M, Young LJ (2005). "Central oxytocin, vasopressin, and corticotropin-releasing factor receptor densities in the basal forebrain predict isolation potentiated startle in rats". J Neurosci. 25 (49): 11479–88. PMID 16339041. doi:10.1523/JNEUROSCI.2524-05.2005.
- Tanaka K, Suzuki M, Sumiyoshi T, Murata M, Tsunoda M, Kurachi M (2003). "Subchronic phencyclidine administration alters central vasopressin receptor binding and social interaction in the rat". J Neurosci. 992 (2): 239–45. PMID 14625062. doi:10.1016/j.brainres.2003.08.050.
- Meyer-Lindenberg A, Kolachana B, Gold B, Olsh A, Nicodemus KK, Mattay V, Dean M, Weinberger Dr (2008). "Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans". Mol. Psychiatry 133 (2): 1–8. PMC 2754603. PMID 18490926. doi:10.1038/mp.2008.54.
- Walum H, Westberg L, Henningsson S, Neiderhiser JM, Reiss D, Igl W, Ganiban JM, Spotts EL, Pedersen NL, Eriksson E, Lichtenstein P (2008). "Genetic variation in the vasopressin receptor 1a gene (AVPR1A) associates with pair-bonding behavior in humans.". PNAS 105 (37): 14153–6. PMC 2533683. PMID 18765804. doi:10.1073/pnas.0803081105.
- Prichard ZM, Mackinnon AJ, Jorm AF, Easteal S (2007). "AVPR1A and OXTR polymorphisms are associated with sexual and reproductive behavioral phenotypes in humans". Hum. Mutat. 28 (11): 1150. PMID 17939166. doi:10.1002/humu.9510.
- Geller B, Tillman R, Badner JA, Cook EH Jr (2005). "Are the arginine vasopressin V1a receptor microsatellites related to hypersexuality in children with prepubertal and early adolescent bipolar disorder phenotype?". Bipolar Disord. 7 (6): 610–6. PMID 16403186. doi:10.1111/j.1399-5618.2005.00259.x.
- Bachner-Melman R, Dina C, Zohar AH, Constantini N, Lerer E, Hoch S, Sella S, Nemanov L, Gritsenko I, Lichtenberg P, Granot R, Ebstein RP (September 2005). "AVPR1a and SLC6A4 gene polymorphisms are associated with creative dance performance". PLoS Genetics 1 (3): e42. PMC 1239939. PMID 16205790. doi:10.1371/journal.pgen.0010042. open access publication - free to read
- Yirmiya N, Rosenberg C, Levi S, Salomon S, Shulman C, Nemanov L, Dina C, Ebstein RP (May 2006). "Association between the arginine vasopressin 1a receptor (AVPR1a) gene and autism in a family-based study: mediation by socialization skills". Molecular Psychiatry 11 (5): 488–94. PMID 16520824. doi:10.1038/sj.mp.4001812.
- Israel S, Lerer E, Shalev I, Uzefovsky F, Reibold M, Bachner-Melman R, Granot R, Bornstein G, Knafo A, Yirmiya N, Ebstein RP (2008). "Molecular genetic studies of the arginine vasopressin 1a receptor (AVPR1a) and the oxytocin receptor (OXTR) in human behaviour: from autism to altruism with some notes in between". Progress in Brain Research 170: 435–49. PMID 18655900. doi:10.1016/S0079-6123(08)00434-2.
- Ukkola LT, Onkamo P, Raijas P, Karma K, Järvelä I (2009). Reif, Andreas, ed. "Musical aptitude is associated with AVPR1A-haplotypes". PLoS ONE 4 (5): e5534. PMC 2678260. PMID 19461995. doi:10.1371/journal.pone.0005534. open access publication - free to read
- Thibonnier M, Coles P, Thibonnier A, Shoham M (2002). "Molecular pharmacology and modeling of vasopressin receptors.". Prog. Brain Res. 139: 179–96. PMID 12436935. doi:10.1016/S0079-6123(02)39016-2.
- Cross SH, Charlton JA, Nan X, Bird AP (1994). "Purification of CpG islands using a methylated DNA binding column.". Nat. Genet. 6 (3): 236–44. PMID 8012384. doi:10.1038/ng0394-236.
- Hirasawa A, Shibata K, Kotosai K, Tsujimoto G (1994). "Cloning, functional expression and tissue distribution of human cDNA for the vascular-type vasopressin receptor.". Biochem. Biophys. Res. Commun. 203 (1): 72–9. PMID 8074728. doi:10.1006/bbrc.1994.2150.
- Thibonnier M, Auzan C, Madhun Z et al. (1994). "Molecular cloning, sequencing, and functional expression of a cDNA encoding the human V1a vasopressin receptor.". J. Biol. Chem. 269 (5): 3304–10. PMID 8106369.
- Young WS, Kovács K, Lolait SJ (1993). "The diurnal rhythm in vasopressin V1a receptor expression in the suprachiasmatic nucleus is not dependent on vasopressin.". Endocrinology 133 (2): 585–90. PMID 8344200. doi:10.1210/en.133.2.585.
- Thibonnier M, Graves MK, Wagner MS et al. (1997). "Structure, sequence, expression, and chromosomal localization of the human V1a vasopressin receptor gene.". Genomics 31 (3): 327–34. PMID 8838314. doi:10.1006/geno.1996.0055.
- North WG, Fay MJ, Longo K, Du J (1998). "Functional vasopressin V1 type receptors are present in variant as well as classical forms of small-cell carcinoma.". Peptides 18 (7): 985–93. PMID 9357056. doi:10.1016/S0196-9781(97)00072-7.
- North WG, Fay MJ, Longo KA, Du J (1998). "Expression of all known vasopressin receptor subtypes by small cell tumors implies a multifaceted role for this neuropeptide.". Cancer Res. 58 (9): 1866–71. PMID 9581826.
- North WG, Fay MJ, Du J (1999). "MCF-7 breast cancer cells express normal forms of all vasopressin receptors plus an abnormal V2R.". Peptides 20 (7): 837–42. PMID 10477084. doi:10.1016/S0196-9781(99)00070-4.
- Tahara A, Tsukada J, Ishii N et al. (1999). "Comparison of vasopressin binding sites in human uterine and vascular smooth muscle cells.". Eur. J. Pharmacol. 378 (1): 137–42. PMID 10478574. doi:10.1016/S0014-2999(99)00403-3.
- Thibonnier M, Graves MK, Wagner MS et al. (2000). "Study of V(1)-vascular vasopressin receptor gene microsatellite polymorphisms in human essential hypertension.". J. Mol. Cell. Cardiol. 32 (4): 557–64. PMID 10756113. doi:10.1006/jmcc.2000.1108.
- Berrada K, Plesnicher CL, Luo X, Thibonnier M (2000). "Dynamic interaction of human vasopressin/oxytocin receptor subtypes with G protein-coupled receptor kinases and protein kinase C after agonist stimulation.". J. Biol. Chem. 275 (35): 27229–37. PMID 10858434. doi:10.1074/jbc.M002288200.
- Kim SJ, Young LJ, Gonen D et al. (2002). "Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism.". Mol. Psychiatry 7 (5): 503–7. PMID 12082568. doi:10.1038/sj.mp.4001125.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "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 99 (26): 16899–903. PMC 139241. PMID 12477932. doi:10.1073/pnas.242603899.
- Tahtaoui C, Balestre MN, Klotz P et al. (2003). "Identification of the binding sites of the SR49059 nonpeptide antagonist into the V1a vasopressin receptor using sulfydryl-reactive ligands and cysteine mutants as chemical sensors.". J. Biol. Chem. 278 (41): 40010–9. PMID 12869559. doi:10.1074/jbc.M301128200.
- Hawtin SR, Wesley VJ, Simms J et al. (2004). "An arginyl in the N-terminus of the V1a vasopressin receptor is part of the conformational switch controlling activation by agonist.". Eur. J. Biochem. 270 (23): 4681–8. PMID 14622255. doi:10.1046/j.1432-1033.2003.03865.x.
- Terrillon S, Barberis C, Bouvier M (2004). "Heterodimerization of V1a and V2 vasopressin receptors determines the interaction with beta-arrestin and their trafficking patterns.". Proceedings of the National Academy of Sciences of the United States of America 101 (6): 1548–53. PMC 341772. PMID 14757828. doi:10.1073/pnas.0305322101.
- Wassink TH, Piven J, Vieland VJ et al. (2005). "Examination of AVPR1A as an autism susceptibility gene.". Mol. Psychiatry 9 (10): 968–72. PMID 15098001. doi:10.1038/sj.mp.4001503.
- Gerhard DS, Wagner L, Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. PMC 528928. PMID 15489334. doi:10.1101/gr.2596504.
- "Symbol Report: AVPR1A". Human Geneome Organization Gene Nomenclature Committee.
- "Vasopressin and Oxytocin Receptors: AVPR1A". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.