Progesterone and mifepristone modify principally the responses of circular myometrium to oxytocin in preparturient rats: comparison with responses to acetylcholine and to calcium.

Jun 1, 1993The Journal of pharmacology and experimental therapeutics

Progesterone and mifepristone mainly change how the uterine muscle ring responds to oxytocin before birth in rats, compared to responses to acetylcholine and calcium

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Abstract

Responses to oxytocin (OT) in the circular myometrium were almost totally abolished by progesterone treatment, while mifepristone restored them to levels seen at spontaneous parturition.

Two populations of oxytocin receptors may exist in the myometrium: one in longitudinal muscle that is constitutive and another in circular muscle that is regulated by progesterone.
Maximal responses to oxytocin in longitudinal myometrial strips were only marginally affected by progesterone or mifepristone treatments compared to control animals.
Progesterone treatment significantly reduced oxytocin responsiveness in the circular myometrium, while mifepristone treatment restored responsiveness.
Responses to acetylcholine were not affected by steroid treatments in either muscle layer.
Calcium ion responses were decreased by progesterone treatment but to a lesser extent than those of oxytocin, and were restored by mifepristone.

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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.

Progesterone and mifepristone modify principally the responses of circular myometrium to oxytocin in preparturient rats: comparison with responses to acetylcholine and to calcium.

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