el Alj A, Winer N, Lallaoui H, Delansorne R, Ferre F, Germain G
Reproduction et Physiopathologie Obstétricale, INSERM U 361, Maternité Baudelocque, Paris, France.
J Pharmacol Exp Ther. 1993 Jun;265(3):1205-12.
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.
我们最近报道，在妊娠大鼠子宫肌层中，合成的OT/AVP V1拮抗剂d(CH2)5[Tyr(Me)2]OVT在子宫肌层纵行条带中对催产素（OT）或精氨酸加压素具有相似的pA2值，在子宫肌层环行条带中对精氨酸加压素也具有相似的pA2值。然而，该拮抗剂在环行条带中对OT无活性，这表明参与OT在环行肌中作用的受体与纵行肌中的OT受体不同。在本研究中，设计了孕酮阻断和孕酮+米非司酮诱导的大鼠分娩模型，以检查孕酮是否在两个子宫肌层中对OT反应性进行不同调节。在器官浴实验中测量对OT的反应，并与去极化子宫肌层条带中对乙酰胆碱和钙离子（Ca2+）的反应进行比较。与妊娠第21天的对照动物相比，来自孕酮或孕酮+米非司酮处理大鼠的纵行切割条带中对OT的最大反应仅受到类固醇处理的轻微影响。相反，孕酮几乎完全消除了环行子宫肌层对OT的反应，而米非司酮处理使反应恢复到自发分娩时的水平。在两个肌层中，对乙酰胆碱的反应不受类固醇处理的影响，对Ca2+的反应在孕酮处理下降低（然而，程度小于OT），并在米非司酮处理后恢复。这些结果表明子宫肌层中存在两种OT受体群体：一种在纵行肌中占主导的组成型受体和一种存在于环行肌中的孕酮调节受体。
