Oxytocin receptor subtypes in the pregnant rat myometrium and decidua: pharmacological differentiations.
Oxytocin (OT) has a dual action in the uterus: a uterotonic action on myometrial cells and a prostaglandin (PG)-releasing action on endometrial/decidual cells. It had not been determined whether the OT-binding sites or receptors on the myometrial and the endometrial/decidual membranes are of the same type or may represent two subtypes. Our studies presented in this paper show that isolated day 19-22 pregnant rat uterine horns and myometrial tissues (uterine horns with decidual tissues removed) incubated in Kreb's buffer at 37 C released PGF2 alpha in sustained quantities into the bathing medium. OT stimulated PG release over the basal release rate in a dose-dependent manner in the whole uterine horn but not in the myometrial tissue. Two OT antagonists, P[Phe(Me)2,Thr4]ornithine vasotocin (antagonist A) and desGly-NH2(9),d(CH2)5(1)[Tyr(Me)2,Thr4]ornithine vasotocin (antagonist B) were found to have different effects on the PG-releasing action of OT. At antiuterotonic doses, antagonist A had no antagonism of the PG-releasing action of OT. On the contrary, antagonist A was found to stimulate uterine PG release. Antagonist B was a full OT antagonist. At equivalent antiuterotonic doses, antagonist B inhibited both the uterotonic action and the PG-releasing action of OT. These findings suggest that OT-sensitive PGs are synthesized/released principally in the endometrium/decidua. The myometrial uterotonic OT receptors and the endometrial/decidual PG-releasing OT receptors are two distinct subtypes and can be differentiated. 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. To be efficacious, OT antagonist therapy needs to block both the uterotonic and the PG-releasing action of OT.
Chan
W Y
WY
Department of Pharmacology, Cornell University Medical College, New York, New York 10021.
Chen
D L
DL
Manning
M
M
D000818:Animals; D003656:Decidua / Q000187:drug effects / Q000502:physiology*; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D009215:Myometrium / Q000187:drug effects / Q000502:physiology*; D009951:Ornipressin / Q000031:analogs & derivatives*; D010121:Oxytocin / Q000031:analogs & derivatives / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000145:classification / Q000502:physiology*; D018045:Receptors, Oxytocin; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*; D014668:Vasotocin / Q000031:analogs & derivatives / Q000494:pharmacology
D011453:Prostaglandins; D011945:Receptors, Angiotensin; D018045:Receptors, Oxytocin; C064578:oxytocin, Pen(1)-(4-MePhe)(2)-Thr(4)-Orn(8)-; C074541:vasotocin, desGly(NH2)(9)d(CH2)5-Tyr(Me)(2)-Thr(4)-Orn(8)-; D009951:Ornipressin; D010121:Oxytocin; D015237:Dinoprost; D015232:Dinoprostone; D014668:Vasotocin