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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
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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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2. Ala Y, Morin D, Mouillac B, Sabatier N, Vargas R, Cotte N, Déchaux M, Antignac C, Arthus MF, Lonergan M et al.. (1998) Functional studies of twelve mutant V2 vasopressin receptors related to nephrogenic diabetes insipidus: molecular basis of a mild clinical phenotype. J Am Soc Nephrol, 9 (10): 1861-72. [PMID:9773787]
3. Albright JD, Reich MF, Delos Santos EG, Dusza JP, Sum FW, Venkatesan AM, Coupet J, Chan PS, Ru X, Mazandarani H et al.. (1998) 5-Fluoro-2-methyl-N-[4-(5H-pyrrolo[2,1-c]-[1, 4]benzodiazepin-10(11H)-ylcarbonyl)-3-chlorophenyl]benzamide (VPA-985): an orally active arginine vasopressin antagonist with selectivity for V2 receptors. J Med Chem, 41 (14): 2442-4. [PMID:9651149]
4. Andrés M, Trueba M, Guillon G. (2002) Pharmacological characterization of F-180: a selective human V(1a) vasopressin receptor agonist of high affinity. Br J Pharmacol, 135 (7): 1828-36. [PMID:11934825]
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7. Breton C, Chellil H, Kabbaj-Benmansour M, Carnazzi E, Seyer R, Phalipou S, Morin D, Durroux T, Zingg H, Barberis C et al.. (2001) Direct identification of human oxytocin receptor-binding domains using a photoactivatable cyclic peptide antagonist: comparison with the human V1a vasopressin receptor. J Biol Chem, 276 (29): 26931-41. [PMID:11337500]
8. Busnelli M, Bulgheroni E, Manning M, Kleinau G, Chini B. (2013) Selective and potent agonists and antagonists for investigating the role of mouse oxytocin receptors. J Pharmacol Exp Ther, 346 (2): 318-27. [PMID:23723434]
9. Cheng LL, Stoev S, Manning M, Derick S, Pena A, Mimoun MB, Guillon G. (2004) Design of potent and selective agonists for the human vasopressin V1b receptor based on modifications of [deamino-cys1]arginine vasopressin at position 4. J Med Chem, 47: 2375-2388. [PMID:15084136]
10. Chini B, Chinol M, Cassoni P, Papi S, Reversi A, Areces L, Marrocco T, Paganelli G, Manning M, Bussolati G. (2003) Improved radiotracing of oxytocin receptor-expressing tumours using the new [111In]-DOTA-Lys8-deamino-vasotocin analogue. Br J Cancer, 89 (5): 930-6. [PMID:12942128]
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]
12. Chini B, Mouillac B, Balestre MN, Trumpp-Kallmeyer S, Hoflack J, Hibert M, Andriolo M, Pupier S, Jard S, Barberis C. (1996) Two aromatic residues regulate the response of the human oxytocin receptor to the partial agonist arginine vasopressin. FEBS Lett, 397 (2-3): 201-6. [PMID:8955347]
13. Cirillo R, Gillio Tos E, Schwarz MK, Quattropani A, Scheer A, Missotten M, Dorbais J, Nichols A, Borrelli F, Giachetti C et al.. (2003) Pharmacology of (2S,4Z)-N-[(2S)-2-hydroxy-2-phenylethyl]-4-(methoxyimino) -1-[(2'-methyl[1,1'-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxamide, a new potent and selective nonpeptide antagonist of the oxytocin receptor. J Pharmacol Exp Ther, 306 (1): 253-61. [PMID:12660315]
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]
16. Crombie AL, Antrilli TM, Campbell BA, Crandall DL, Failli AA, He Y, Kern JC, Moore WJ, Nogle LM, Trybulski EJ. (2010) Synthesis and evaluation of azabicyclo[3.2.1]octane derivatives as potent mixed vasopressin antagonists. Bioorg Med Chem Lett, 20 (12): 3742-5. [PMID:20471258]
17. de Wied D, Diamant M, Fodor M. (1993) Central nervous system effects of the neurohypophyseal hormones and related peptides. Front Neuroendocrinol, 14 (4): 251-302. [PMID:8258377]
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]
20. Failli AA, Shumsky JS, Steffan RJ, Caggiano TJ, Williams DK, Trybulski EJ, Ning X, Lock Y, Tanikella T, Hartmann D et al.. (2006) Pyridobenzodiazepines: a novel class of orally active, vasopressin V2 receptor selective agonists. Bioorg Med Chem Lett, 16 (4): 954-9. [PMID:16297621]
21. Foord SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP, Spedding M, Harmar AJ. (2005) International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev, 57 (2): 279-88. [PMID:15914470]
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23. Griffante C, Green A, Curcuruto O, Haslam CP, Dickinson BA, Arban R. (2005) Selectivity of d[Cha4]AVP and SSR149415 at human vasopressin and oxytocin receptors: evidence that SSR149415 is a mixed vasopressin V1b/oxytocin receptor antagonist. Br J Pharmacol, 146: 744-751. [PMID:16158071]
24. Iijima M, Yoshimizu T, Shimazaki T, Tokugawa K, Fukumoto K, Kurosu S, Kuwada T, Sekiguchi Y, Chaki S. (2014) Antidepressant and anxiolytic profiles of newly synthesized arginine vasopressin V1B receptor antagonists: TASP0233278 and TASP0390325. Br J Pharmacol, 171 (14): 3511-25. [PMID:24654684]
25. Jasper JR, Harrell CM, O'Brien JA, Pettibone DJ. (1995) Characterization of the human oxytocin receptor stably expressed in 293 human embryonic kidney cells. Life Sci, 57 (24): 2253-61. [PMID:7475979]
26. Kimura T, Makino Y, Saji F, Takemura M, Inoue T, Kikuchi T, Kubota Y, Azuma C, Nobunaga T, Tokugawa Y et al.. (1994) Molecular characterization of a cloned human oxytocin receptor. Eur J Endocrinol, 131 (4): 385-90. [PMID:7921228]
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]
30. Marchingo AJ, Abrahams JM, Woodcock EA, Smith AI, Mendelsohn FA, Johnston CI. (1988) Properties of [3H]1-desamino-8-D-arginine vasopressin as a radioligand for vasopressin V2-receptors in rat kidney. Endocrinology, 122 (4): 1328-36. [PMID:2964362]
31. McCafferty GP, Pullen MA, Wu C, Edwards RM, Allen MJ, Woollard PM, Borthwick AD, Liddle J, Hickey DM, Brooks DP et al.. (2007) Use of a novel and highly selective oxytocin receptor antagonist to characterize uterine contractions in the rat. Am J Physiol Regul Integr Comp Physiol, 293 (1): R299-305. [PMID:17395790]
32. Nakamura S, Yamamura Y, Itoh S, Hirano T, Tsujimae K, Aoyama M, Kondo K, Ogawa H, Shinohara T, Kan K et al.. (2000) Characterization of a novel nonpeptide vasopressin V(2)-agonist, OPC-51803, in cells transfected human vasopressin receptor subtypes. Br J Pharmacol, 129 (8): 1700-6. [PMID:10780976]
33. Pena A, Murat B, Trueba M, Ventura MA, Wo NC, Szeto HH, Cheng LL, Stoev S, Guillon G, Manning M. (2007) Design and synthesis of the first selective agonists for the rat vasopressin V(1b) receptor: based on modifications of deamino-[Cys1]arginine vasopressin at positions 4 and 8. J Med Chem, 50: 835-847. [PMID:17300166]
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35. Saito M, Tahara A, Sugimoto T. (1997) 1-desamino-8-D-arginine vasopressin (DDAVP) as an agonist on V1b vasopressin receptor. Biochem Pharmacol, 53: 1711-1717. [PMID:9264324]
36. Serradeil-Le Gal C, Lacour C, Valette G, Garcia G, Foulon L, Galindo G, Bankir L, Pouzet B, Guillon G, Barberis C et al.. (1996) Characterization of SR 121463A, a highly potent and selective, orally active vasopressin V2 receptor antagonist. J Clin Invest, 98 (12): 2729-38. [PMID:8981918]
37. Serradeil-Le Gal C, Raufaste D, Double-Cazanave E, Guillon G, Garcia C, Pascal M, Maffrand JP. (2000) Binding properties of a selective tritiated vasopressin V2 receptor antagonist, [H]-SR 121463. Kidney Int, 58 (4): 1613-22. [PMID:11012895]
38. Serradeil-Le Gal C, Valette G, Foulon L, Germain G, Advenier C, Naline E, Bardou M, Martinolle J-P, Pouzet B, Raufaste D, Garcia C, Double-Cazenave E, Pauly M, Pascal M, Barbier A, Scatton B, Maffrand J-P, Le Fur G. (2004) SSR126768A (4-Chloro-3-[(3R)-(+)-5-chloro-1-(2,4-dimethoxybenzyl)-3-methyl-2oxo-2,3-dihydro-1H-indol-3-yl]-N-ethyl-N-(3-pyridylmethyl)-benzamidine, hydrochloride): a new selective and orally active oxytocin receptor antagonist for the prevention of preterm labor. J Pharmacol Exp Therap, 309: 414-424. [PMID:14722330]
39. Serradeil-Le Gal C, Wagnon J, Simiand J, Griebel G, Lacour C, Guillon G, Barberis C, Brossard G, Soubrie P, Nisato D, Pascal M, Pruss R, Scatton B, Maffrand JP, Le Fur G. (2002) Characterization of (2S,4R)-1-[5-chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxy-phenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N,N-dimethyl-2-pyrrolidine carboxamide (SSR149415), a selective and orally active vasopressin V1b receptor antagonist. J Pharmacol Exp Ther, 300: 1122-1130. [PMID:11861823]
40. Tahara A, Saito M, Sugimoto T, Tomura Y, Wada K, Kusayama T, Tsukada J, Ishii N, Yatsu T, Uchida W et al.. (1998) Pharmacological characterization of YM087, a potent, nonpeptide human vasopressin V1A and V2 receptor antagonist. Naunyn Schmiedebergs Arch Pharmacol, 357 (1): 63-9. [PMID:9459574]
41. Tahara A, Saito M, Sugimoto T, Tomura Y, Wada K, Kusayama T, Tsukada J, Ishii N, Yatsu T, Uchida W et al.. (1998) Pharmacological characterization of the human vasopressin receptor subtypes stably expressed in Chinese hamster ovary cells. Br J Pharmacol, 125 (7): 1463-70. [PMID:9884074]
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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 SPH, Christopoulos A, Davenport AP, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors. Br J Pharmacol. 180 Suppl 2:S23-S144.
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).