Agonist and antagonist specificities of decidual prostaglandin-releasing oxytocin receptors and myometrial uterotonic oxytocin receptors in pregnant rats.
This paper describes further pharmacological characterization of the decidual prostaglandin-releasing oxytocin receptors and the myometrial uterotonic oxytocin receptors in the uterus of the pregnant rat. The effects of oxytocin, arginine-vasopressin and their related agonists and antagonists on the release of PGF2 alpha were studied in vitro on isolated uteri from rats on day 19-20 of pregnancy that had been incubated in Krebs buffer, pH 7.4, at 37 degrees C. The concentration of PGF2 alpha in the media was measured using specific radioimmunoassays. It was found that the decidual and myometrial oxytocin receptors exhibit different ligand specificities. Of the agonists tested, oxytocin and arginine-vasopressin stimulated PGF2 alpha release in a dose-dependent manner. Arginine-vasopressin has only 3% of the uterotonic potency of oxytocin, but was found to have 16% of its PGF2 alpha-releasing activity. [4-Threonine, 7-glycine]oxytocin, a highly potent and selective uterotonic oxytocin analogue, had no detectable prostaglandin-releasing activity at a dosage 30 times higher than oxytocin. However, 1-deamino-[8-D-arginine]vasopressin, a highly potent and selective antidiuretic arginine-vasopressin analogue, which has only 10% of the uterotonic activity of arginine-vasopressin, was as potent as arginine-vasopressin in prostaglandin-releasing activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Chen
D L
DL
Department of Pharmacology, Cornell University Medical College, New York, NY 10021.
Chan
W Y
WY
Manning
M
M
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D003894:Deamino Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D003656:Decidua / Q000378:metabolism*; D015237:Dinoprost / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D009215:Myometrium / Q000378:metabolism*; D009924:Organ Culture Techniques; D010121:Oxytocin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical
D018045:Receptors, Oxytocin; D001127:Arginine Vasopressin; D010121:Oxytocin; C007223:vasopressin, 1-deamino-4-Val-8-Arg-; C028799:argipressin, deaminopenicillamine(1)-Val(4)-; D015237:Dinoprost; D003894:Deamino Arginine Vasopressin