Oxytocin- and vasopressin-binding sites in the rat uterus: Competition binding and inhibitory pa2 studies with oxytocin and oxytocin antagonists

W. Y. Chan, Lin Cao, Patricia S. Hill, Victor J. Hruby

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Recent reports have presented evidence suggesting that there are distinct oxytocin (OT) and vasopressin (VP) receptors in the human and rabbit myometrium. In this study we have investigated whether OT and arginine vasopressin (AVP) activate the same or two different receptor systems in the rat uterus in producing their uterotonic action and whether the myometrial OT/VP receptors are similar to the V1receptors in the vascular smooth muscle cells. We compared the dose-response characteristics of OT and AVP by the in vitro cumulative dose-response curve technique. We determined the ligand-receptor binding characteristics of [3H]OT and [3H]AVP on uterine membrane fractions from nonpregnant and pregnant rats. Specific OT antagonists were used in competition receptor binding assays and in antioxytocic pA2bioassays against OT and AVP to determine whether OT antagonists can discriminate between OT- and AVP-binding sites in the myometrium. We also compared the in vitro antioxytocic (OT receptor-mediated action) and the in vivo antivasopressor (V1receptor-mediated action) potencies of a series of six OT antagonists. Our results show that OT- and AVP-binding sites in the nonpregnant rat uterus have similar binding characteristics and cannot be distinguished by the dose-response study, radioligand receptor binding assays, or OT antagonists in the competition binding and pA2assays. However, in the term pregnant parturient uterus, the two binding sites can be clearly differentiated. OT receptor density, but not AVP, was markedly increased at term pregnancy. All six OT antagonists studied in this investigation were more potent in antagonizing the uterotonic response to OT than the vasopressor response to AVP. The antioxytocic:rantivasopressor potency ratios, however, were different between the antagonists, ranging from nearly equal (0.91) to low (0.1). The results above suggest that there are distinct OT- and AVP-binding sites in the rat myometrium. The myometrial OT/ AVP receptors are similar to but not the same as the V1receptors in the vascular smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)2095-2101
Number of pages7
JournalEndocrinology
Volume126
Issue number4
DOIs
StatePublished - Apr 1990

ASJC Scopus subject areas

  • Endocrinology

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