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. 2009 Nov;158(Suppl 1):S99–S100. doi: 10.1111/j.1476-5381.2009.00501_64.x

Vasopressin and oxytocin

PMCID: PMC2884675

Overview: Vasopressin (AVP) and oxytocin (OT) receptors (nomenclature as agreed by NC-IUPHAR Subcommittee on Vasopressin and Oxytoxcin Receptors) are activated by the endogenous cyclic nonapeptides AVP and OT. These peptides are derived from precursors (ENSG00000101200 and ENSG00000101405 respectively), which also produce neurophysins.

Nomenclature V1a V1b V2 OT
Ensembl ID ENSG00000166148 P47901 ENSG00000126895 ENSG00000180914
Principal transduction Gq/11 Gq/11 Gs Gq/11, Gi/o
Rank order of potency AVP > OT AVP > OT AVP > OT OT ≥ AVP
Selective agonists F180, [Phe2,Orn8]VT d[D-3-Pal2]VP, d(Cha4]AVP (Derick et al., 2002), d[Leu4,Lys8]VP (Pena et al., 2007) d[Val4,DArg8]VP, OPC51803, VNA932 [Thr4,Gly7]OT (Elands et al., 1988)
Selective antagonists d(CH2)5[Tyr(Me)2,Arg8]VP (9.0), SR49059 (8.9), YM087 (8.2) SSR149415 (8.4; Griebel et al., 2002; Serradeil-Le Gal et al., 2002) VPA985 (8.9; Albright et al., 1998), d(CH2)5[D-Ile2, Ile4]AVP (8.4), SR121463A (8.4; Serradeil-Le Gal et al., 1996), OPC31260 (7.6; Yamamura et al., 1992), YM087 (8.96) SSR126768A (9.3; Serradeil-Le Gal et al., 2004), desGlyNH2-d(CH2)5[Tyr(Me)2,Thr4,Orn8]OT (8.5), L372662 (8.4),
Probes [3H]-AVP, [3H]-SR49059 (1.5 nM), [3H]-d(CH2)5[Tyr(Me)2,Arg8]AVP (1.1 nM), [125I]-HO-Phaa,D-Tyr(Me)-Phe-Gln-Asn-Arg-Pro-Arg-NH2 (50 pM) [3H]-AVP, [3H]-SSR149415 (1 nM; Serradeil-Le Gal et al., 2007) [3H]-AVP, [3H]-desGly-NH2[D-Ile2,Ile4]AVP (2.8 nM), [3H]-d[D-Arg8]AVP (0.8 nM), [3H]-SR121463A (4.1 nM) [3H]-OT, [35S]-non-peptide OT antagonist (42 pM; Lemaire et al., 2002), [125I]-d(CH2)5[Tyr(Me)2, Thr4,Orn8,Tyr-NH29]OVT (90 pM), [111In]-DOTA-dLVT (4.5 nM; Chini et al., 2003)
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The V2 receptor exhibits marked species differences, such that many ligands (d(CH2)5[D-Ile2,Ile4]VP and [3H]-desGly-NH2[D-Ile2,Ile4]VP) exhibit low affinity at human V2 receptors (Ala et al., 1997). Similarly, [3H]-d[D-Arg8]VP is V2-selective in the rat, not in the human (Saito et al., 1997). The gene encoding the V2 receptor is polymorphic in man, underlying nephrogenic diabetes insipidus (Bichet, 1998). YM087 display high affinity for both human V1a and V2 receptors (Tahara et al., 1998). d[Cha4]AVP is selective only for the human and bovine V1b receptors (Derick et al., 2002), while d[Leu4,Lys8]VP has high affinity for the rat V1b receptor (Pena et al., 2007).

Glossary

Abbreviations:

[111In]-DOTA-dLVT

[111In]-DOTA-Lys8-deamino-vasotocin

[35S]-non-peptide OT antagonist

[35S]-(1-(1-(2-(2,2,2-trifluoroethoxy)-4-(1-methylsulfonyl-4-piperidinyloxy)phenylacetyl)-4-piperidinyl)-3,4-dihydro-2(1H)-quinolinone)

F180

Hmp-Phe-Ile-Hgn-Asn-Cys-Pro-Dab(Abu)-Gly-NH2

L372662

1-(1-{4-[1-(2-methyl-1-oxidopyridin-3-ylmethyl)piperidin-4-yloxyl]-2-methoxybenzoyl}piperidin-4-yl)-1,4-dihydrobenz[d][1,3]]oxazin-2one

OPC31260

5-dimethylamino-1-(4-[2-methylbenzoylamino]benzoyl)-2,3,4,5-tetrahydro-1H-benzazepine

OPC51803

(5r)-2-(1-[2-chloro-4-{1-pyrrolidinyl}benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepin-5-yl)-N-isopropylacetamide

SR121463A

1-(4-Boc-2-methoxybenzenesulfonyl)-5-ethoxy-3-spiro-(4-[2-morpholinoethoxy]cyclohexane)indol-2-one fumarate; equatorial isomer

SR49059

(2s)-1-([2r,3s]-[5-chloro-3-{chlorophenyl}-1-{3,4-dimethoxysulfonyl}-3-hydroxy]-2,3-dihydro-1H-indole-2-carbonyl)-pyrrolidine-2-carboxamide

SSR149415

(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

SSR126768A

4-chloro-3-[(3R)-(+)-5-chloro-1-(2,4-dimethoxybenzyl)-3-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]-N-ethyl-N-(3-pyridylmethyl)-benzamide, hydrochloride

VNA932

(2-chloro-4-[3-methyl-pyrazol-1-yl]-phenyl)-(5H,11H)-pyrrolo(2,1-c)(1,4)benzodiazepin-10-yl-methanone

VPA985

5-fluoro-2-methyl-N-(4-[5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylcarbonyl]-3-chlorophenyl)benzamide

YM087

(4′-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin-6-yl) carbonyl]-2-phenylbenzanilide monohydrochloride)

Further Reading

Ali F, Guglin M, Vaitkevicius P, Ghali JK (2007). Therapeutic potential of vasopressin receptor antagonists. Drugs67: 847–858.

Arai Y, Fujimori A, Sudoh K, Sasamata M (2007). Vasopressin receptor antagonists: potential indications and clinical results. Curr Opin Pharmacol7: 124–129.

Arthur P, Taggart MJ, Mitchell BF (2007). Oxytocin and parturition: a role for increased myometrial calcium and calcium sensitization? Front Biosci12: 619–633.

Carter CS (2007). Sex differences in oxytocin and vasopressin: implications for autism spectrum disorders? Behav Brain Res176: 170–186.

Gimpl G, Reitz J, Brauer S, Trossen C (2008). Oxytocin receptors: ligand binding, signalling and cholesterol dependence. Prog Brain Res170: 193–204.

Lemmens-Gruber R, Kamyar M (2006). Vasopressin antagonists. Cell Mol Life Sci63: 1766–1779.

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 Pharmacol154: 358–368.

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 Res170: 473–512.

Rossi J, Orlandi C, Gheorghiade M (2007). Vasopressin antagonists in the management of heart failure. Expert Rev Cardiovasc Ther5: 323–330.

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