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Vasopressin and oxytocin receptors C
Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Overview
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Vasopressin (AVP) and oxytocin (OT) receptors (nomenclature as recommended by NC-IUPHAR [21]) are activated by the endogenous cyclic nonapeptides vasopressin (AVP, P01185) and oxytocin (OXT, P01178). These peptides are derived from precursors which also produce neurophysins (neurophysin I for oxytocin; neurophysin II for vasopressin). Vasopressin and oxytocin differ at only 2 amino acids (positions 3 and 8). There are metabolites of these neuropeptides that may be biologically active [17].
Receptors
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V1A receptor
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V1B receptor
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V2 receptor
C
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OT receptor
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Further reading
* Key recommended reading is highlighted with an asterisk
Bartz JA, Zaki J, Bolger N, Ochsner KN. (2011) Social effects of oxytocin in humans: context and person matter. Trends Cogn Sci (Regul. Ed.), 15 (7): 301-9. [PMID:21696997]
* Carter CS, Kenkel WM, MacLean EL, Wilson SR, Perkeybile AM, Yee JR, Ferris CF, Nazarloo HP, Porges SW, Davis JM et al.. (2020) Is Oxytocin "Nature's Medicine"?. Pharmacol Rev, 72 (4): 829-861. [PMID:32912963]
Gimpl G, Reitz J, Brauer S, Trossen C. (2008) Oxytocin receptors: ligand binding, signalling and cholesterol dependence. Prog Brain Res, 170: 193-204. [PMID:18655883]
* Gulliver D, Werry E, Reekie TA, Katte TA, Jorgensen W, Kassiou M. (2019) Targeting the Oxytocin System: New Pharmacotherapeutic Approaches. Trends Pharmacol Sci, 40 (1): 22-37. [PMID:30509888]
* Knepper MA. (2012) Systems biology in physiology: the vasopressin signaling network in kidney. Am J Physiol, Cell Physiol, 303 (11): C1115-24. [PMID:22932685]
* Koshimizu TA, Nakamura K, Egashira N, Hiroyama M, Nonoguchi H, Tanoue A. (2012) Vasopressin V1a and V1b receptors: from molecules to physiological systems. Physiol Rev, 92 (4): 1813-64. [PMID:23073632]
Lee HJ, Macbeth AH, Pagani JH, Young WS. (2009) Oxytocin: the great facilitator of life. Prog Neurobiol, 88 (2): 127-51. [PMID:19482229]
* Manning M, Misicka A, Olma A, Bankowski K, Stoev S, Chini B, Durroux T, Mouillac B, Corbani M, Guillon G. (2012) Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics. J Neuroendocrinol, 24 (4): 609-28. [PMID:22375852]
Manning M, Stoev S, Chini B, Durroux T, Mouillac B, Guillon G. (2008) Peptide and non-peptide agonists and antagonists for the vasopressin and oxytocin V1a, V1b, V2 and OT receptors: research tools and potential therapeutic agents. Prog Brain Res, 170: 473-512. [PMID:18655903]
McGregor IS, Callaghan PD, Hunt GE. (2008) From ultrasocial to antisocial: a role for oxytocin in the acute reinforcing effects and long-term adverse consequences of drug use?. Br J Pharmacol, 154 (2): 358-68. [PMID:18475254]
Meyer-Lindenberg A, Domes G, Kirsch P, Heinrichs M. (2011) Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine. Nat Rev Neurosci, 12 (9): 524-38. [PMID:21852800]
Neumann ID, Landgraf R. (2012) Balance of brain oxytocin and vasopressin: implications for anxiety, depression, and social behaviors. Trends Neurosci, 35 (11): 649-59. [PMID:22974560]
Oghlakian G, Klapholz M. (2009) Vasopressin and vasopressin receptor antagonists in heart failure. Cardiol Rev, 17 (1): 10-5. [PMID:19092365]
* Rigney N, de Vries GJ, Petrulis A, Young LJ. (2022) Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities. Endocrinology, 163 (9). [PMID:35863332]
Roper J, O'Carroll AM, Young W, Lolait S. (2011) The vasopressin Avpr1b receptor: molecular and pharmacological studies. Stress, 14 (1): 98-115. [PMID:20828336]
* Russell JA. (2018) Fifty Years of Advances in Neuroendocrinology. Brain Neurosci Adv, 2: 2398212818812014. DOI: doi: 10.1177/2398212818812014 [PMID:32166160]
Veeraveedu PT, Palaniyandi SS, Yamaguchi K, Komai Y, Thandavarayan RA, Sukumaran V, Watanabe K. (2010) Arginine vasopressin receptor antagonists (vaptans): pharmacological tools and potential therapeutic agents. Drug Discov Today, 15 (19-20): 826-41. [PMID:20708094]
References
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11. Chini B, Mouillac B, Ala Y, Balestre MN, Trumpp-Kallmeyer S, Hoflack J, Elands J, Hibert M, Manning M, Jard S et al.. (1995) Tyr115 is the key residue for determining agonist selectivity in the V1a vasopressin receptor. EMBO J, 14 (10): 2176-82. [PMID:7774575]
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14. Cotte N, Balestre MN, Aumelas A, Mahé E, Phalipou S, Morin D, Hibert M, Manning M, Durroux T, Barberis C et al.. (2000) Conserved aromatic residues in the transmembrane region VI of the V1a vasopressin receptor differentiate agonist vs. antagonist ligand binding. Eur J Biochem, 267 (13): 4253-63. [PMID:10866830]
15. Cotte N, Balestre MN, Phalipou S, Hibert M, Manning M, Barberis C, Mouillac B. (1998) Identification of residues responsible for the selective binding of peptide antagonists and agonists in the V2 vasopressin receptor. J Biol Chem, 273 (45): 29462-8. [PMID:9792651]
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18. Derick S, Cheng LL, Voirol MJ, Stoev S, Giacomini M, Wo NC, Szeto HH, Ben Mimoun M, Andres M, Gaillard RC et al.. (2002) [1-deamino-4-cyclohexylalanine] arginine vasopressin: a potent and specific agonist for vasopressin V1b receptors. Endocrinology, 143 (12): 4655-64. [PMID:12446593]
19. Elands J, Barberis C, Jard S. (1988) [3H]-[Thr4,Gly7]OT: a highly selective ligand for central and peripheral OT receptors. Am J Physiol, 254 (1 Pt 1): E31-8. [PMID:2827511]
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27. Koga K, Nagai Y, Hanyu M, Yoshinaga M, Chaki S, Ohtake N, Ozaki S, Zhang MR, Suhara T, Higuchi M. (2017) High-Contrast PET Imaging of Vasopressin V1B Receptors with a Novel Radioligand, 11C-TASP699. J Nucl Med, 58 (10): 1652-1658. [PMID:28450560]
28. Laporte R, Kohan A, Heitzmann J, Wisniewska H, Toy J, La E, Tariga H, Alagarsamy S, Ly B, Dykert J et al.. (2011) Pharmacological characterization of FE 202158, a novel, potent, selective, and short-acting peptidic vasopressin V1a receptor full agonist for the treatment of vasodilatory hypotension. J Pharmacol Exp Ther, 337 (3): 786-96. [PMID:21411496]
29. Liddle J, Allen MJ, Borthwick AD, Brooks DP, Davies DE, Edwards RM, Exall AM, Hamlett C, Irving WR, Mason AM et al.. (2008) The discovery of GSK221149A: a potent and selective oxytocin antagonist. Bioorg Med Chem Lett, 18 (1): 90-4. [PMID:18032036]
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NC-IUPHAR subcommittee and family contributors
Subcommittee members:
Stephen Lolait (Chairperson)
Bernard Mouillac (Past chairperson)
Daniel Bichet
Michel Bouvier
Bice Chini
Gerald Gimpl
Gilles Guillon
Tadashi Kimura
Mark Knepper
Maurice Manning
Anne-Marie O'Carroll
Claudine Serradeil-Le Gal
Joseph G. Verbalis
Mark Wheatley
Hans H. Zingg |
Other contributors:
Melvyn Soloff |
How to cite this family page
Database page citation (select format):
Concise Guide to PHARMACOLOGY citation:
Alexander SP, Christopoulos A, Davenport AP, Kelly E, Mathie A, Peters JA, Veale EL et al. (2021) THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors. Br J Pharmacol. 176 Suppl 1:S27-S156.
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Vasopressin and OT receptors have a characteristic and sometimes overlapping distribution in a number of tissues including brain. There are phylogenetic, ontogenetic and sex-specific differences in the levels and distribution of these receptors, particularly in the brain. The V2 receptor exhibits marked species differences, such that many ligands (d(CH2)5[D-Ile2,Ile4]AVP and [3H]desGly-NH2[D-Ile2,Ile4]VP) exhibit low affinity at human V2 receptors [2]. Similarly, desmopressin (dDAVP) is more V2 selective in the rat than in the human [35]. The gene encoding the V2 receptor is polymorphic in man, underlying nephrogenic diabetes insipidus [6]. Agonist d[Cha4]AVP is selective only for the human and bovine V1B receptors [18], while d[Leu4]LVP has high affinity for the rat V1B receptor [33]. There are a group of V1B receptor antagonists - TASP0233278, TASP0380325 and TASP0434299 that exhibit good selectivity profiles (human, rat) [24,27]. Agonist and antagonist selectivity for the OT receptor may vary in different species, as shown for Thr4Gly7OT in mice, rats and humans [8]. Knockouts of vasopressin and OT receptors have system-specific defects (e.g., impaired ability to concentrate urine in V2 receptor knockouts) which include behavioural deficits (principally in V1A, V1B and OT receptor knockouts).