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Gene Review

Oxtr  -  oxytocin receptor

Rattus norvegicus

Synonyms: OT-R, OTR, OTR1, Otr, Oxytocin receptor
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Disease relevance of Oxtr

  • Hypertension and exercise training differentially affect oxytocin and oxytocin receptor expression in the brain [1].
  • In trained WKY, baseline bradycardia (P<0.05) occurred simultaneously with increased NTS OT immunostaining and mRNA expression (+3.5-fold), without any change in OT receptor mRNA expression [1].
  • To study the molecular mechanisms underlying OTR regulation, we have isolated and characterized recombinant bacteriophage lambda EMBL3 genomic clones containing the rat OTR gene, using sequence information derived from a human myometrial OTR cDNA [2].
  • The existence of two OT receptor subtypes in the uterus has important implications in the clinical application of OT antagonists as tocolytics for preterm labor [3].
  • The goal of the present study was to determine whether systemic administration of an OT receptor antagonist would attenuate the increase in PRA that is normally evoked by arterial hypotension in rats [4].

Psychiatry related information on Oxtr


High impact information on Oxtr

  • Inhibition of oxytocin receptor function by direct binding of progesterone [9].
  • These effects are highly steroid- and receptor-specific, because binding and signalling functions of the closely related human OTR are not affected by P4 itself but by the P4 metabolite 5beta-dihydroprogesterone [9].
  • The selective oxytocin receptor agonist [Thr4, Gly7] oxytocin does not stimulate cAMP production in RIMCT cells but does promote PI hydrolysis [10].
  • These studies demonstrate that AVP or a V2 receptor agonist stimulate PI hydrolysis in cultured RIMCT cells via occupancy of the oxytocin receptor [10].
  • Moreover, when Tyr115 is replaced by an Asp and a Phe, the amino acids naturally occurring in the V2 and in the OT receptor subtypes, the agonist selectivity of the V1a receptor switches accordingly [11].

Chemical compound and disease context of Oxtr


Biological context of Oxtr


Anatomical context of Oxtr


Associations of Oxtr with chemical compounds


Physical interactions of Oxtr

  • Cotreatment with P4 strongly reduced OT binding by 75% (P < 0.01) but did not significantly affect the E2-induced rise in OTR mRNA (11% decrease, P > 0.1) [22].
  • The present study shows that testosterone treatment of aging rats restores normal adult levels of OT receptor binding in the olfactory tubercle and in the hypothalamic ventromedial nucleus, but not in the caudate-putamen [23].

Regulatory relationships of Oxtr

  • An extremely high proportion of neurons expressing either ER also coexpress mRNA for the oxytocin receptor (OTR) [24].
  • As it is known that transforming growth factor-beta (TGF-beta) can be released from carrier proteins by acid or heat, TGF-beta1 and 2 were tested and found to induce an increase of OTR binding [25].
  • The objective of the present study was to further elucidate our previous observation that beta2-adrenoceptor activation induces oxytocin receptor (OTR) expression in rat myometrium [26].

Other interactions of Oxtr


Analytical, diagnostic and therapeutic context of Oxtr


  1. Hypertension and exercise training differentially affect oxytocin and oxytocin receptor expression in the brain. Martins, A.S., Crescenzi, A., Stern, J.E., Bordin, S., Michelini, L.C. Hypertension (2005) [Pubmed]
  2. Structure, characterization, and expression of the rat oxytocin receptor gene. Rozen, F., Russo, C., Banville, D., Zingg, H.H. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  3. Oxytocin receptor subtypes in the pregnant rat myometrium and decidua: pharmacological differentiations. Chan, W.Y., Chen, D.L., Manning, M. Endocrinology (1993) [Pubmed]
  4. Oxytocin antagonist disrupts hypotension-evoked renin secretion and other responses in conscious rats. Huang, W., Sjöquist, M., Skott, O., Stricker, E.M., Sved, A.F. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2001) [Pubmed]
  5. Oxytocin antagonism alters rat dams' oral grooming and upright posturing over pups. Pedersen, C.A., Boccia, M.L. Physiol. Behav. (2003) [Pubmed]
  6. The inhibition of oxytocin-induced grooming by a specific receptor antagonist. Drago, F., Sarnyai, Z., D'Agata, V. Physiol. Behav. (1991) [Pubmed]
  7. Effects of two stressors on behaviour in the elevated X-maze: preliminary investigation of their interaction with 8-OH-DPAT. McBlane, J.W., Handley, S.L. Psychopharmacology (Berl.) (1994) [Pubmed]
  8. Variations in maternal behaviour are associated with differences in oxytocin receptor levels in the rat. Francis, D.D., Champagne, F.C., Meaney, M.J. J. Neuroendocrinol. (2000) [Pubmed]
  9. Inhibition of oxytocin receptor function by direct binding of progesterone. Grazzini, E., Guillon, G., Mouillac, B., Zingg, H.H. Nature (1998) [Pubmed]
  10. Vasopressin-stimulated phosphoinositide hydrolysis in cultured rat inner medullary collecting duct cells is mediated by the oxytocin receptor. Teitelbaum, I. J. Clin. Invest. (1991) [Pubmed]
  11. Tyr115 is the key residue for determining agonist selectivity in the V1a vasopressin receptor. Chini, B., Mouillac, B., Ala, Y., Balestre, M.N., Trumpp-Kallmeyer, S., Hoflack, J., Elands, J., Hibert, M., Manning, M., Jard, S. EMBO J. (1995) [Pubmed]
  12. Uterine leiomyomas express myometrial contractile-associated proteins involved in pregnancy-related hormone signaling. Cesen-Cummings, K., Houston, K.D., Copland, J.A., Moorman, V.J., Walker, C.L., Davis, B.J. J. Soc. Gynecol. Investig. (2003) [Pubmed]
  13. Coupling of oxytocin receptor to G proteins in rat myometrium during labor: Gi receptor interaction. Strakova, Z., Soloff, M.S. Am. J. Physiol. (1997) [Pubmed]
  14. 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. Cirillo, R., Gillio Tos, E., Schwarz, M.K., Quattropani, A., Scheer, A., Missotten, M., Dorbais, J., Nichols, A., Borrelli, F., Giachetti, C., Golzio, L., Marinelli, P., Thomas, R.J., Chevillard, C., Laurent, F., Portet, K., Barberis, C., Chollet, A. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  15. Oxytocin receptors and parturition. I. Control of oxytocin receptor concentration in the rat myometrium at term. Alexandrova, M., Soloff, M.S. Endocrinology (1980) [Pubmed]
  16. Oxytocin receptor messenger ribonucleic acid: characterization, regulation, and cellular localization in the rat pituitary gland. Breton, C., Pechoux, C., Morel, G., Zingg, H.H. Endocrinology (1995) [Pubmed]
  17. Oxytocin receptor gene expression in rat mammary gland: structural characterization and regulation. Breton, C., Di Scala-Guenot, D., Zingg, H.H. J. Mol. Endocrinol. (2001) [Pubmed]
  18. Oxytocin and its receptors are synthesized in the rat vasculature. Jankowski, M., Wang, D., Hajjar, F., Mukaddam-Daher, S., McCann, S.M., Gutkowska, J. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  19. Rat oxytocin receptor in brain, pituitary, mammary gland, and uterus: partial sequence and immunocytochemical localization. Adan, R.A., Van Leeuwen, F.W., Sonnemans, M.A., Brouns, M., Hoffman, G., Verbalis, J.G., Burbach, J.P. Endocrinology (1995) [Pubmed]
  20. Oxytocin receptor binding in the hypothalamus during gestation in rats. Bealer, S.L., Lipschitz, D.L., Ramoz, G., Crowley, W.R. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
  21. Cocaine treatment alters oxytocin receptor binding but not mRNA production in postpartum rat dams. Jarrett, T.M., McMurray, M.S., Walker, C.H., Johns, J.M. Neuropeptides (2006) [Pubmed]
  22. Oxytocin receptor gene expression in the rat uterus during pregnancy and the estrous cycle and in response to gonadal steroid treatment. Larcher, A., Neculcea, J., Breton, C., Arslan, A., Rozen, F., Russo, C., Zingg, H.H. Endocrinology (1995) [Pubmed]
  23. Region-specific effect of testosterone on oxytocin receptor binding in the brain of the aged rat. Arsenijevic, Y., Tribollet, E. Brain Res. (1998) [Pubmed]
  24. Sex and estrogenic effects on coexpression of mRNAs in single ventromedial hypothalamic neurons. Devidze, N., Mong, J.A., Jasnow, A.M., Kow, L.M., Pfaff, D.W. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  25. Neurons modulate oxytocin receptor expression in rat cultured astrocytes: involvement of TGF-beta and membrane components. Mittaud, P., Labourdette, G., Zingg, H., Guenot-Di Scala, D. Glia (2002) [Pubmed]
  26. Up-regulation of oxytocin receptors in non-pregnant rat myometrium by isoproterenol: effects of steroids. Engstrom, T., Bratholm, P., Christensen, N.J., Vilhardt, H. J. Endocrinol. (1999) [Pubmed]
  27. Changes of receptor mRNAs for oxytocin and estrogen during the estrous cycle in rat uterus. Murata, T., Narita, K., Honda, K., Higuchi, T. J. Vet. Med. Sci. (2003) [Pubmed]
  28. Oxytocin-stimulated release of adrenocorticotropin from the rat pituitary is mediated by arginine vasopressin receptors of the V1b type. Schlosser, S.F., Almeida, O.F., Patchev, V.K., Yassouridis, A., Elands, J. Endocrinology (1994) [Pubmed]
  29. Effects of RU486 on estrogen, progesterone, oxytocin, and their receptors in the rat uterus during late gestation. Fang, X., Wong, S., Mitchell, B.F. Endocrinology (1997) [Pubmed]
  30. Beta2-adrenoceptor desensitization in non-pregnant estrogen-primed rat myometrium involves modulation of oxytocin receptor gene expression. Engstrøm, T., Bratholm, P., Vilhardt, H., Christensen, N.J. J. Mol. Endocrinol. (1998) [Pubmed]
  31. Differential regulation of estrogen receptor alpha and beta mRNAs in the rat uterus during pregnancy and labor: possible involvement of estrogen receptors in oxytocin receptor regulation. Murata, T., Narita, K., Honda, K., Matsukawa, S., Higuchi, T. Endocr. J. (2003) [Pubmed]
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