Alternative titles; symbols
HGNC Approved Gene Symbol: AVPR1B
Cytogenetic location: 1q32.1 Genomic coordinates (GRCh38): 1:206,106,936-206,117,388 (from NCBI)
The neurohypophyseal hormone arginine vasopressin (AVP) induces diverse actions, including stimulation of hepatic glycogenolysis, contraction of vascular smooth muscle cells and mesangial cells, antidiuresis in the kidney, and aggregation of platelets. These actions of AVP are mediated through specific G protein-coupled receptors. AVP receptors are classified into at least 3 subtypes: V1a, V1b, and V2. The V1a receptor (600821) has been localized in the liver, vascular smooth muscle, brain, mesangial cells, and platelets. The V2 receptor (300538) is exclusively expressed in the kidney, and defects in this receptor result in nephrogenic diabetes insipidus. Sugimoto et al. (1994) cloned the V1b receptor from a cDNA library of human pituitary. (The gene is also referred to as AVPR3.) AVP modulates the release of ACTH, beta-endorphin, and prolactin from the anterior pituitary. Release is mediated by the V1b receptor through the mobilization of intracellular Ca(2+) by phosphatidylinositol hydrolysis. The deduced 424-amino acid sequence of the V1b receptor had highest overall homology with the V1a, V2, and oxytocin receptors, with homologies of 45, 39, and 45%, respectively. Expressed in COS-1 cells, V1b had a single binding site for AVP. It bound various agonists and antagonists of vasopressin with affinities distinct from those of V1a and V2 receptors but consistent with those anticipated for the V1b receptor on the basis of pharmacologic studies.
The AVPR1B gene was also cloned by de Keyzer et al. (1994), who referred to it as AVPR3.
Rousseau-Merck et al. (1995) mapped the gene to 1q32 by fluorescence in situ hybridization.
Birnbaumer (2000) noted that the biologic effects of AVP are mediated by 3 receptor subtypes: the V1A and V1B receptors that activate phospholipases via Gq/11, and the V2 receptor that activates adenylyl cyclase by interacting with GS. Isolation of the cDNAs encoding the V1A and V1B receptor subtypes explained the tissue variability of V1 antagonist binding, whereas identification of the cDNA and gene encoding the V2 receptor provided the information to identify the mutations responsible for X-linked nephrogenic diabetes insipidus (304800). Mutations that abrogate the production and/or release of AVP from the pituitary have diabetes insipidus as their most dramatic manifestation, indicating that the maintenance of water homeostasis is the most important physiologic role of this neuropeptide.
The pituitary V3 vasopressin receptor was used by de Keyzer et al. (1996) to analyze the corticotroph phenotype of secreting bronchial carcinoids associated with the ectopic ACTH syndrome. Ectopic ACTH secretion occurs in highly differentiated and rather indolent tumors such as bronchial carcinoids or, in contrast, in various types of aggressive and poorly differentiated neuroendocrine tumors. They found that in 6 of 8 bronchial carcinoids responsible for the ectopic ACTH syndrome, both proopiomelanocortin (176830) and the V3 receptor gene were expressed at the same level as they are in ACTH-secreting pituitary adenomas; in contrast, no POMC expression and only very faint V3 receptor expression were detected in 6 of 8 nonsecreting bronchial carcinoids.
Wersinger et al. (2002) found that mice with a targeted disruption of the V1br gene, which is expressed in brain, exhibited marked reduction in aggression and modest impairment in social recognition. The mice performed normally in all other behaviors examined, including sexual behavior, suggesting that reduced aggression and social memory are not simply the results of a global deficit in sensorimotor function or motivation. Wersinger et al. (2002) suggested that V1br antagonists may be useful for the treatment of aggressive behaviors.
Tanoue et al. (2004) investigated the functional role of the V1b receptor in vivo by using gene targeting to create a mouse model lacking the V1br gene. Under resting conditions, circulating concentrations of ACTH and corticosterone were lower in the null mice compared with wildtype mice. The normal increase in circulating ACTH levels in response to exogenous administration of AVP was impaired in the null mice, whereas corticotropin-releasing hormone-stimulated ACTH release was not impaired. The increase in ACTH after a forced swim stress was significantly suppressed in the null mice. The results demonstrated that the V1b receptor plays a crucial role in regulating hypothalamic-pituitary-adrenal axis activity. It does this by maintaining ACTH and corticosterone levels, not only under stress but also under basal conditions.
Yamaguchi et al. (2013) found that circadian rhythms of behavior (locomotor activity), clock gene expression, and body temperature immediately reentrained to phase-shifted light-dark cycles in mice lacking V1a (AVPR1A; 600821) and V1b. Nevertheless, the behavior of V1a-V1b double-knockout mice was still coupled to the internal clock, which oscillated normally under standard conditions. Experiments with suprachiasmatic nucleus (SCN) slices in culture suggested that interneuronal communication mediated by V1a and V1b confers on the SCN an intrinsic resistance to external perturbation. Pharmacologic blockade of V1a and V1b in the SCN of wildtype mice resulted in accelerated recovery from jet lag.
Birnbaumer, M. Vasopressin receptors. TEM 11: 406-410, 2000. [PubMed: 11091117] [Full Text: https://doi.org/10.1016/s1043-2760(00)00304-0]
de Keyzer, Y., Auzan, C., Lenne, F., Beldjord, C., Thibonnier, M., Bertagna, X., Clauser, E. Cloning and characterization of the human Ve pituitary vasopressin receptor. FEBS Lett. 356: 215-220, 1994. [PubMed: 7805841] [Full Text: https://doi.org/10.1016/0014-5793(94)01268-7]
de Keyzer, Y., Lenne, F., Auzan, C., Jegou, S., Rene, P., Vaudry, H., Kuhn, J.-M., Luton, J.-P., Clauser, E., Bertagna, X. The pituitary V3 vasopressin receptor and the corticotroph phenotype in ectopic ACTH syndrome. J. Clin. Invest. 97: 1311-1318, 1996. [PubMed: 8636444] [Full Text: https://doi.org/10.1172/JCI118547]
Rousseau-Merck, M.-F., Rene, P., Derre, J., Bienvenu, T., Berger, R., de Keyzer, Y. Chromosomal localization of the human V3 pituitary vasopressin receptor gene (AVPR3) to 1q32. Genomics 30: 405-406, 1995. [PubMed: 8586456]
Sugimoto, T., Saito, M., Mochizuki, S., Watanabe, Y., Hashimoto, S., Kawashima, H. Molecular cloning and functional expression of a cDNA encoding the human V(1b) vasopressin receptor. J. Biol. Chem. 269: 27088-27092, 1994. [PubMed: 7929452]
Tanoue, A., Ito, S., Honda, K., Oshikawa, S., Kitagawa, Y., Koshimizu, T., Mori, T., Tsujimoto, G. The vasopressin V1b receptor critically regulates hypothalamic-pituitary-adrenal axis activity under both stress and resting conditions. J. Clin. Invest. 113: 302-309, 2004. [PubMed: 14722621] [Full Text: https://doi.org/10.1172/JCI19656]
Wersinger, S. R., Ginns, E. I., O'Carroll, A.-M., Lolait, S. J., Young, W. S., III. Vasopressin V1b receptor knockout reduces aggressive behavior in male mice. Molec. Psychiat. 7: 975-984, 2002. [PubMed: 12399951] [Full Text: https://doi.org/10.1038/sj.mp.4001195]
Yamaguchi, Y., Suzuki, T., Mizoro, Y., Kori, H., Okada, K., Chen, Y., Fustin, J.-M., Yamazaki, F., Mizuguchi, N., Zhang, J., Dong, X., Tsujimoto, G., Okuno, Y., Doi, M., Okamura, H. Mice genetically deficient in vasopressin V1a and V1b receptors are resistant to jet lag. Science 342: 85-90, 2013. [PubMed: 24092737] [Full Text: https://doi.org/10.1126/science.1238599]