V1a vasopressin receptor

• V1aバソプレシン受容体、V1aバソプレシンレセプター

関

V1 receptor、V1b vasopressin receptor、V2 receptor、vasopressin receptor

WordNet

1. hormone secreted by the posterior pituitary gland (trade name Pitressin) and also by nerve endings in the hypothalamus; affects blood pressure by stimulating capillary muscles and reduces urine flow by affecting reabsorption of water by kidney tubules (同)antidiuretic_hormone, ADH, Pitressin
2. a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response
3. the 22nd letter of the Roman alphabet (同)v

PrepTutorEJDIC

1. =sense organ / 受信装置
2. V1号[ロケット爆弾](第二次世界大戦中,ドイツ軍が英国攻撃用に使った)
3. vanadium の化学記号

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/27 01:29:45」(JST)

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Arginine vasopressin receptor 1A
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1YTV
Identifiers
Symbols	AVPR1A ; AVPR V1a; AVPR1; V1aR
External IDs	OMIM: 600821 MGI: 1859216 HomoloGene: 568 IUPHAR: 366 ChEMBL: 1889 GeneCards: AVPR1A Gene
Gene ontology Molecular function • vasopressin receptor activity • protein kinase C binding • protein binding • peptide hormone binding • V1A vasopressin receptor binding • peptide binding Cellular component • endosome • cytosol • plasma membrane • integral component of plasma membrane • cytoplasmic vesicle Biological process • regulation of systemic arterial blood pressure by vasopressin • maternal aggressive behavior • positive regulation of systemic arterial blood pressure • generation of precursor metabolites and energy • G-protein coupled receptor signaling pathway • activation of phospholipase C activity • positive regulation of cytosolic calcium ion concentration • negative regulation of female receptivity • grooming behavior • blood circulation • positive regulation of cell proliferation • positive regulation of heart rate • positive regulation of glutamate secretion • myotube differentiation • calcium-mediated signaling • telencephalon development • positive regulation of cell growth • positive regulation of prostaglandin biosynthetic process • positive regulation of cellular pH reduction • cellular response to hormone stimulus • social behavior • positive regulation of renal sodium excretion • cellular response to water deprivation • maternal behavior • sperm ejaculation • penile erection • positive regulation of vasoconstriction • response to corticosterone • negative regulation of transmission of nerve impulse • response to peptide Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	552	54140
Ensembl	ENSG00000166148	ENSMUSG00000020123
UniProt	P37288	Q62463
RefSeq (mRNA)	NM_000706	NM_016847
RefSeq (protein)	NP_000697	NP_058543
Location (UCSC)	Chr 12: 63.14 – 63.15 Mb	Chr 10: 122.45 – 122.45 Mb
PubMed search	[1]	[2]

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.

Ligand binding

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 (K_i = 1.2 ± 0.2 nM)
• Relcovaptan (SR-49059) (K_i = 1.3 ± 0.2 nM)
• AVP (K_i = 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 (K_i = 68 ± 17 nM)
• Oxytocin (K_i = 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

The activity / genetic variants of the AVPR1A gene might be related to generosity and altruistic behavior. NatureNews has referred to AVPR1A as the "ruthlessness gene".

Prairie vs. montane voles

The injection of oxytocin (OXT) vs. oxytocin antagonist (OTA) at birth has sexually dimorphic effects in prairie voles later on in life in various areas of the brain.

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.

Mice

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).

Although activation of Avpr1a is a major mediator of anxiogenesis in males, it is not in females.

Rats

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.

Humans

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.

Polymorphisms

RS3

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.

RS1

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.

Other microsatellites

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 AVPR_1A 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.

References

Further reading

• Thibonnier M, Coles P, Thibonnier A, Shoham M (2002). "Molecular pharmacology and modeling of vasopressin receptors.". Prog. Brain Res. 139: 179–96. doi:10.1016/S0079-6123(02)39016-2. PMID 12436935. 
• 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. doi:10.1038/ng0394-236. PMID 8012384. 
• 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. doi:10.1006/bbrc.1994.2150. PMID 8074728. 
• 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. doi:10.1210/en.133.2.585. PMID 8344200. 
• 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. doi:10.1006/geno.1996.0055. PMID 8838314. 
• 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. doi:10.1016/S0196-9781(97)00072-7. PMID 9357056. 
• 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. doi:10.1016/S0196-9781(99)00070-4. PMID 10477084. 
• 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. doi:10.1016/S0014-2999(99)00403-3. PMID 10478574. 
• 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. doi:10.1006/jmcc.2000.1108. PMID 10756113. 
• 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. doi:10.1074/jbc.M002288200. PMID 10858434. 
• 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. doi:10.1038/sj.mp.4001125. PMID 12082568. 
• 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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. 
• 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. doi:10.1074/jbc.M301128200. PMID 12869559. 
• 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. doi:10.1046/j.1432-1033.2003.03865.x. PMID 14622255. 
• 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. doi:10.1073/pnas.0305322101. PMC 341772. PMID 14757828. 
• Wassink TH, Piven J, Vieland VJ et al. (2005). "Examination of AVPR1A as an autism susceptibility gene.". Mol. Psychiatry 9 (10): 968–72. doi:10.1038/sj.mp.4001503. PMID 15098001. 
• 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. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. 

External links

• "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. 

UpToDate Contents

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English Journal

• Highly potent antidiuretic antagonists: conformational studies of vasopressin analogues modified with 1-naphthylalanine enantiomers at position 2.

• Lubecka EA, Ciarkowski J, Prahl A, Sikorska E.SourceFaculty of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland.
• Chemical biology & drug design.Chem Biol Drug Des.2012 Jun;79(6):1033-42. doi: 10.1111/j.1747-0285.2012.01358.x. Epub 2012 Mar 16.
• In this paper, we investigated the structure-activity relationship of two vasopressin analogues, [Cpa(1) ,(L-1-Nal)(2) ]AVP (I) and [Cpa(1) ,(D-Nal)(2) ]AVP (II) by NMR spectroscopy and molecular modeling. Both peptides exhibit antioxytocic and antipressor potency. Inversion of configuration of the
• PMID 22321057

• V1a receptor agonists: The search for clean and green alternatives to vasopressin*.

• van Haren FM, Mitchell I.SourceThe Canberra Hospital, Canberra, Australia.
• Critical care medicine.Crit Care Med.2012 Jun;40(6):1999-2000.
• PMID 22610225

Japanese Journal

• Therapeutic Potential of Vasopressin-Receptor Antagonists in Heart Failure

• Izumi Yasukatsu,Miura Katsuyuki,Iwao Hiroshi
• Journal of Pharmacological Sciences, 2014
• … Arginine vasopressin (AVP) is a 9-amino acid peptide that is secreted from the posterior pituitary in response to high plasma osmolality and hypotension. … AVP has important roles in circulatory and water homoeostasis, which are mediated by oxytocin receptors and by AVP receptor subtypes: V1a (mainly vascular), V1b (pituitary), and V2 (renal). … Vaptans are orally and intravenously active nonpeptide vasopressin-receptor antagonists. …
• NAID 130003382634

• The roles of V1a vasopressin receptors in blood pressure homeostasis : a review of studies on V1a receptor knockout mice

• FUJIWARA Yoko,TANOUE Akito,TSUJIMOTO Gozoh,KOSHIMIZU Taka-aki
• Clinical and experimental nephrology 16(1), 30-34, 2012-02-01
• NAID 10030342354

• 精神機能におけるバソプレシン受容体の役割

• 江頭 伸昭,三島 健一,岩崎 克典 [他],中西 博,大石 了三,藤原 道弘
• 日本薬理学雑誌 134(1), 3-7, 2009-07-01
• … 循環系の恒常性の維持に重要な役割を果たしていることが知られている．AVPの受容体は，V1a，V1bおよびV2受容体の3つのサブタイプに分類されており，特にV1aおよびV1b受容体は大脳皮質や海馬など脳内に広く分布していることから，中枢における役割が注目されている．そこで本稿では，V1aおよびV1b受容体欠損マウスを用いた著者らの研究成果を紹介するとともに，精神機能にお …
• NAID 10025740988

Related Links

• Arginine vasopressin receptor 1A - Wikipedia, the free encyclopedia

V1a vasopressin receptor; antidiuretic hormone receptor 1A; SCCL vasopressin subtype 1a receptor; V1-vascular .... "Molecular cloning, sequencing, and functional expression of a cDNA encoding the human V1a vasopressin receptor".

• V1a vasopressin receptors maintain normal blood pressure by ...

16 May 2006 ... Although AVP is used clinically as a potent vasoconstrictor (V1a receptor- mediated) in patients with circulatory shock, the physiological role of vasopressin V1a receptors in blood pressure (BP) homeostasis is ill-defined.

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★リンクテーブル★

リンク元	「V1aバソプレシン受容体」「V1b vasopressin receptor」「V1aバソプレシンレセプター」
関連記事	「V1」「V」「vasopressin receptor」

「V1aバソプレシン受容体」

　　[★]

英

V1a vasopressin receptor

関

バソプレッシン受容体、バソプレシンレセプター、V1受容体、V2レセプター、V1aバソプレシンレセプター、V1bバソプレシンレセプター

「V1b vasopressin receptor」

　　[★]

• V1bバソプレシン受容体、V1bバソプレシンレセプター

関

V1 receptor、V1a vasopressin receptor、V2 receptor、vasopressin receptor

「V1aバソプレシンレセプター」

　　[★]

英

V1a vasopressin receptor

関

V1aバソプレシン受容体

「V1」

　　[★]

• 心電図：V1でRの振幅が上昇していたら：右室肥大、右脚ブロック、WPW症候群、純後壁梗塞(YN.C-25)

　

「V」

　　[★]

• バリン valine
• ビタミン vitamine
• ventilation

　 　

「vasopressin receptor」

　　[★] バソプレシン受容体