Vasopressin receptor 1A

Last updated
AVPR1A
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases AVPR1A , AVPR V1a, AVPR1, V1aR, arginine vasopressin receptor 1A
External IDs OMIM: 600821 MGI: 1859216 HomoloGene: 568 GeneCards: AVPR1A
Orthologs
SpeciesHumanMouse
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: 122.28 – 122.29 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Vasopressin receptor 1A (V1AR), or arginine vasopressin receptor 1A (officially called AVPR1A) is one of the three major receptor types for 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. [5]

Contents

V1AR is also known as:

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. [5] [6] 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 antidiuretic 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. [7]

Competitors of [125I]Tyr-Phaa-specific binding to AVPR1A include: [6]

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. [8]

Role in behavior

The activity/genetic variants of the AVPR1A gene might be related to generosity and altruistic behavior. [9] Nature News has referred to AVPR1A as the "ruthlessness gene". [10]

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. [11]

Males treated with OXT showed increases in Avpr1a in the ventral pallidum, 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. [11]

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. [12]

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. [13] Some studies have shown Avpr1a knockout mice to have deficits in their circadian rhythms [14] [15] and olfaction. [14]

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. [16] However, conflicting results have been found in another study. [14] Also, unlike vasopressin 1b receptor and oxytocin knockout mice, Avpr1a KO mice have a normal Bruce effect (appropriate failure of pregnancy in presence of novel male). [17]

Although activation of Avpr1a is a major mediator of anxiogenesis in males, it is not in females. [18]

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. [19]

Rats with reduced Avpr1a in the bed nucleus of the stria terminalis have increased incidences[ spelling? ] of the isolation potentiated startle, a measure of isolation-induced anxiety. [20]

Subchronic phencyclidine (PCP) treatment (which induces symptoms similar to those of schizophrenia) reduces Avpr1a density in many brain regions, implying there might be a role for AVPR1A in schizophrenia. [21]

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. [5]

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. [22]

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.

A 2015 study found a correlation between AVPR1A expression and predisposition to extra-pair mating in women but not in men. [23]

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. [24]

In a study of 203 male and female university students, participants with short (308–325 bp) vs. long (327–343) 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. [9]

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. [22]

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. [22]

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. [25] However, there is no evidence of preferential transmission of AVPR1A microsatellite repeats to hypersexual or uninhibited people-seeking. [26]

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. [27] [28] [29] [30]

Chimpanzee 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. [31]

Related Research Articles

<span class="mw-page-title-main">Vasopressin</span> Mammalian hormone released from the pituitary gland

Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travels down the axon terminating in the posterior pituitary, and is released from vesicles into the circulation in response to extracellular fluid hypertonicity (hyperosmolality). AVP has two primary functions. First, it increases the amount of solute-free water reabsorbed back into the circulation from the filtrate in the kidney tubules of the nephrons. Second, AVP constricts arterioles, which increases peripheral vascular resistance and raises arterial blood pressure.

<span class="mw-page-title-main">Oxytocin</span> Peptide hormone and neuropeptide

Oxytocin is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. Present in animals since early stages of evolution, in humans it plays roles in behavior that include social bonding, reproduction, childbirth, and the period after childbirth. Oxytocin is released into the bloodstream as a hormone in response to sexual activity and during labour. It is also available in pharmaceutical form. In either form, oxytocin stimulates uterine contractions to speed up the process of childbirth. In its natural form, it also plays a role in maternal bonding and milk production. Production and secretion of oxytocin is controlled by a positive feedback mechanism, where its initial release stimulates production and release of further oxytocin. For example, when oxytocin is released during a contraction of the uterus at the start of childbirth, this stimulates production and release of more oxytocin and an increase in the intensity and frequency of contractions. This process compounds in intensity and frequency and continues until the triggering activity ceases. A similar process takes place during lactation and during sexual activity.

<span class="mw-page-title-main">Supraoptic nucleus</span> ADH secreting nucleus of the hypothalamus.

The supraoptic nucleus (SON) is a nucleus of magnocellular neurosecretory cells in the hypothalamus of the mammalian brain. The nucleus is situated at the base of the brain, adjacent to the optic chiasm. In humans, the SON contains about 3,000 neurons.

<span class="mw-page-title-main">MECP2</span> DNA-binding protein involved in methylation

MECP2 is a gene that encodes the protein MECP2. MECP2 appears to be essential for the normal function of nerve cells. The protein seems to be particularly important for mature nerve cells, where it is present in high levels. The MECP2 protein is likely to be involved in turning off several other genes. This prevents the genes from making proteins when they are not needed. Recent work has shown that MECP2 can also activate other genes. The MECP2 gene is located on the long (q) arm of the X chromosome in band 28 ("Xq28"), from base pair 152,808,110 to base pair 152,878,611.

<span class="mw-page-title-main">Pair bond</span> Biological term

In biology, a pair bond is the strong affinity that develops in some species between a mating pair, often leading to the production and rearing of young and potentially a lifelong bond. Pair-bonding is a term coined in the 1940s that is frequently used in sociobiology and evolutionary biology circles. The term often implies either a lifelong socially monogamous relationship or a stage of mating interaction in socially monogamous species. It is sometimes used in reference to human relationships.

<span class="mw-page-title-main">Vasopressin receptor 1B</span> Protein-coding gene in the species Homo sapiens

Vasopressin V1b receptor (V1BR) also known as vasopressin 3 receptor (VPR3) or antidiuretic hormone receptor 1B is a protein that in humans is encoded by the AVPR1B gene.

<span class="mw-page-title-main">Vasopressin receptor 2</span> Protein-coding gene in the species Homo sapiens

Vasopressin receptor 2 (V2R), or arginine vasopressin receptor 2, is a protein that acts as receptor for vasopressin. AVPR2 belongs to the subfamily of G-protein-coupled receptors. Its activity is mediated by the Gs type of G proteins, which stimulate adenylate cyclase.

<span class="mw-page-title-main">Beta-1 adrenergic receptor</span> Protein-coding gene in the species Homo sapiens

The beta-1 adrenergic receptor, also known as ADRB1, can refer to either the protein-encoding gene or one of the four adrenergic receptors. It is a G-protein coupled receptor associated with the Gs heterotrimeric G-protein that is expressed predominantly in cardiac tissue. In addition to cardiac tissue, beta-1 adrenergic receptors are also expressed in the cerebral cortex.

The actions of vasopressin are mediated by stimulation of tissue-specific G protein-coupled receptors (GPCRs) called vasopressin receptors that are classified into the V1 (V1A), V2, and V3 (V1B) receptor subtypes. These three subtypes differ in localization, function and signal transduction mechanisms.

<span class="mw-page-title-main">Preoptic area</span> Region of the anterior hypothalamus

The preoptic area is a region of the hypothalamus. MeSH classifies it as part of the anterior hypothalamus. TA lists four nuclei in this region,.

<span class="mw-page-title-main">Vasotocin</span> Chemical compound

Vasotocin is an oligopeptide homologous to oxytocin and vasopressin found in all non-mammalian vertebrates and possibly in mammals during the fetal stage of development. Arginine vasotocin (AVT), a hormone produced by neurosecretory cells within the posterior pituitary gland (neurohypophysis) of the brain, is a major endocrine regulator of water balance and osmotic homoeostasis and is involved in social and sexual behavior in non-mammalian vertebrates. In mammals, it appears to have biological properties similar to those of oxytocin and vasopressin. It has been found to have effects on the regulation of REM sleep. Evidence for the existence of endogenous vasotocin in mammals is limited and no mammalian gene encoding vasotocin has been confirmed.

<span class="mw-page-title-main">Oxytocin receptor</span> Genes on human chromosome 3

The oxytocin receptor, also known as OXTR, is a protein which functions as receptor for the hormone and neurotransmitter oxytocin. In humans, the oxytocin receptor is encoded by the OXTR gene which has been localized to human chromosome 3p25.

<span class="mw-page-title-main">PER3</span> Protein and coding gene in humans

The PER3 gene encodes the period circadian protein homolog 3 protein in humans. PER3 is a paralog to the PER1 and PER2 genes. It is a circadian gene associated with delayed sleep phase syndrome in humans.

<span class="mw-page-title-main">Angiotensin II receptor type 1</span> Protein-coding gene in the species Homo sapiens

Angiotensin II receptor type 1(AT1) is a Gq/11-coupled G protein-coupled receptor (GPCR) and the best characterized angiotensin receptor. It is encoded in humans by the AGTR1 gene. AT1 has vasopressor effects and regulates aldosterone secretion. It is an important effector controlling blood pressure and volume in the cardiovascular system. Angiotensin II receptor blockers are drugs indicated for hypertension, diabetic nephropathy and congestive heart failure.

5-HT<sub>1A</sub> receptor Serotonin receptor protein distributed in the cerebrum and raphe nucleus

The serotonin 1A receptor is a subtype of serotonin receptors, or 5-HT receptors, that binds serotonin, also known as 5-HT, a neurotransmitter. 5-HT1A is expressed in the brain, spleen, and neonatal kidney. It is a G protein-coupled receptor (GPCR), coupled to the Gi protein, and its activation in the brain mediates hyperpolarization and reduction of firing rate of the postsynaptic neuron. In humans, the serotonin 1A receptor is encoded by the HTR1A gene.

<span class="mw-page-title-main">WAY-267464</span> Chemical compound

WAY-267464 is a potent, selective, non-peptide agonist for the oxytocin receptor, with negligible affinity for the vasopressin receptors. Contradictorily however, though originally described as selective for the oxytocin receptor and lacking affinity for the vasopressin receptors, it has since been reported to also act as a potent vasopressin V1A receptor antagonist. WAY-267464 has been shown to cross the blood–brain barrier to a significantly greater extent than exogenously applied oxytocin, and in animal tests produces centrally-mediated oxytocinergic actions such as anxiolytic effects, but with no antidepressant effect evident. It was developed by a team at Ferring Pharmaceuticals. WAY-267464 was under investigation for the potential clinical treatment of anxiety disorders by Wyeth, and reached the preclinical stage of development, but no development has been reported as of 2011.

The biology of trust is the study of physiological mechanisms involved in mediating trust in social attachments. It has been studied in terms of genetics, endocrinology and neurobiology.

Zoe R. Donaldson is an American neuroscientist and assistant professor at the University of Colorado Boulder. Donaldson explores the neurobiological and genetic mechanisms of social bonding and social behavior in rodents. Her work will help to elucidate how variations in genetics and circuit activity across the population predispose certain individuals to mental illness. Donaldson is a pioneer in the use of the monogamous prairie voles to study social behaviors and has been developing novel genetic tools, since her graduate work at Emory University, to study voles in the lab to better understand the neural circuits underlying pair bonding.

<span class="mw-page-title-main">AVP gene</span> Gene

Arginine Vasopressin (AVP) Gene is a gene whose product is proteolytically cleaved to produce vasopressin, neurophysin II, and a glycoprotein called copeptin. AVP and other AVP-like peptides are found in mammals, as well as mollusks, arthropods, nematodes, and other invertebrate species. In humans, AVP is present on chromosome 20 and plays a role in homeostatic regulation. The products of AVP have many functions that include vasoconstriction, regulating the balance of water in the body, and regulating responses to stress. Expression of AVP is regulated by the Transcription Translation Feedback Loop (TTFL), which is an important part of the circadian system that controls the expression of clock genes. AVP has important implications in the medical field as its products have significant roles throughout body.

<span class="mw-page-title-main">LIT-001</span> Chemical compound

LIT-001 is a small-molecule oxytocin receptor agonist and vasopressin receptor mixed agonist and antagonist that was first described in the literature in 2018. Along with TC OT 39 and WAY-267464, it is one of the first small-molecule oxytocin receptor agonists to have been developed. LIT-001 has greatly improved pharmacokinetic properties relative to oxytocin, reduces social deficits in animal models, and may have potential as a therapeutic agent in the treatment of social disorders like autism in humans.

References

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  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020123 - Ensembl, May 2017
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  26. ↑ Geller B, Tillman R, Badner JA, Cook EH (Dec 2005). "Are the arginine vasopressin V1a receptor microsatellites related to hypersexuality in children with a prepubertal and early adolescent bipolar disorder phenotype?". Bipolar Disorders. 7 (6): 610–6. doi:10.1111/j.1399-5618.2005.00259.x. PMID   16403186.
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  30. ↑ Ukkola LT, Onkamo P, Raijas P, Karma K, Järvelä I (2009). Reif A (ed.). "Musical aptitude is associated with AVPR1A-haplotypes". PLOS ONE. 4 (5): e5534. Bibcode:2009PLoSO...4.5534U. doi: 10.1371/journal.pone.0005534 . PMC   2678260 . PMID   19461995. Open Access logo PLoS transparent.svg
  31. ↑ Donaldson ZR, Kondrashov FA, Putnam A, Bai Y, Stoinski TL, Hammock EA, Young LJ (Jun 2008). "Evolution of a behavior-linked microsatellite-containing element in the 5' flanking region of the primate AVPR1A gene". BMC Evolutionary Biology . 8 180: 180. doi: 10.1186/1471-2148-8-180 . PMC   2483724 . PMID   18573213.

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