Modulation of cyclic AMP content of the rat myometrium: desensitization to isoproterenol, PGE2 and prostacyclin.
Exposure of the oestrogen-dominated rat myometrium to either isoproterenol or PGE2 resulted in a rapid but transient accumulation of cyclic AMP, with a progressive loss of responsiveness to the corresponding agonist. Induction of refractoriness was a time- and dose-related phenomenon. In the earliest time, desensitization was agonist-specific but was followed, with continued exposure, by a cross desensitization between isoproterenol and PGE2 and vice versa. Differential time courses for development and reversal of specific and heterologous refractoriness indicate at least 2 different processes for the 2 phenomena, the non-specific type being possibly mediated by cyclic AMP. Exposure to isoproterenol or PGE2 also caused an attenuated cyclic AMP response to prostacyclin (PGI2). Kinetics for PGE2-induced desensitization to PGI2 were comparable to that of an agonist-specific refractoriness, indicating that PGE2 and PGI2 may share common receptor sites. PGF2 alpha, PGD2 and 6-keto PGF1 alpha, which contract the myometrium but are ineffective on adenylate-cyclase activity, did not promote cyclic AMP refractoriness to PGE2, PGI2 or isoproterenol. Isoproterenol also caused refractoriness to its own relaxing activity, whereas PGE2 did not affect isoproterenol-induced relaxation despite a marked attenuation of the beta-adrenergic response to cyclic AMP. These results provide further evidence for the non-exclusive role of cyclic AMP in mediating uterine relaxation.
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology*; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism; D011453:Prostaglandins / Q000494:pharmacology*; D011457:Prostaglandins D / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*; D011460:Prostaglandins F / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013997:Time Factors; D014599:Uterus / Q000187:drug effects*
D011453:Prostaglandins; D011457:Prostaglandins D; D011458:Prostaglandins E; D011460:Prostaglandins F; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D011464:Epoprostenol; D000242:Cyclic AMP; D007545:Isoproterenol