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. V1AR 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 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. 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 The activity / genetic variants of the AVPR1A gene might be related to generosity and altruistic behavior. Nature News 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