Progesterone and mifepristone modify principally the responses of circular myometrium to oxytocin in preparturient rats: comparison with responses to acetylcholine and to calcium.
We have recently reported that in the pregnant rat myometrium the synthetic OT/AVP V1 antagonist d(CH2)5[Tyr(Me)2]OVT has similar pA2 values against oxytocin (OT) or arginine vasopressin in longitudinal myometrial strips and against arginine vasopressin in circular myometrial strips. However, the antagonist is inactive against OT in circular strips, suggesting that the receptor involved in the action of OT in circular muscle is distinct from the OT receptor in longitudinal muscle. In this study, models of progesterone-blocked and progesterone + mifepristone-induced rat parturition were designed to check whether progesterone modulated OT responsiveness differentially in the two myometrial layers. Responses to OT were measured in organ bath experiments and compared with responses to acetylcholine and to calcium ions (Ca2+) in depolarized myometrial strips. Compared with control animals at day 21 of pregnancy, maximal responses to OT in longitudinally cut strips from progesterone- or progesterone + mifepristone-treated rats were only marginally affected by steroid treatments. In contrast, progesterone almost totally abolished responses to OT in the circular myometrium, whereas mifepristone treatment restored responses to those seen at spontaneous parturition. In both muscle layers, responses to acetylcholine were unaffected by steroid treatments and those to Ca2+ were decreased by progesterone treatment (however, to a lesser extent than those of OT) and were restored by mifepristone. These results suggest the presence of two populations of OT receptors in the myometrium: a constitutive type of receptor predominent in longitudinal muscle and a progesterone-regulated receptor present in circular muscle.
Reproduction et Physiopathologie Obstétricale, INSERM U 361, Maternité Baudelocque, Paris, France.
A
A
el Alj
N
N
Winer
H
H
Lallaoui
R
R
Delansorne
F
F
Ferre
G
G
Germain
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D066298:In Vitro Techniques; D007751:Labor, Induced; D015735:Mifepristone / Q000494:pharmacology*; D009215:Myometrium / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects
D011976:Receptors, Muscarinic; D015735:Mifepristone; D011374:Progesterone; D010121:Oxytocin; D009543:Nifedipine; D000109:Acetylcholine; D002118:Calcium