Interactions of substances which induce contractions (prostaglandins, oxytocin) and of epinephrine, which induces relaxation, with the adenylate cyclase system were examined in estrogen-treated rat myometrium. Epinephrine and prostaglandin E1 (PGE1) (also PGE2) stimulated adenylate cyclase activity. The response to both agents was very rapid, being detectable at 30 sec. Propranolol inhibited the activation of adenylate cyclase by epinephrine but not that by PGE1. A single adenylate cyclase appeared to be involved in stimulation by both agonists. PGF1α, PGF2α, and oxytocin had no significant effect on adenosine cyclic 3',5'-monophosphate (cAMP) concentrations. All the E and F prostaglandins analysed elicited contractions in rat uteri; therefore PGE1 stimulated contractions although elevating cAMP levels. Epinephrine antagonized contractions evoked by PFG2α and oxytocin as well as by PGE1. The relaxing effect of epinephrine could be mimicked by dibutyryl-cAMP and inhibited by propranolol. There seemed to be a good correlation between the stimulation of adenylate cyclase by epinephrine and its effect on motility, implicating a role for cAMP in smooth muscle relaxation. Such a correlation could not be demonstrated for PGE1. Two prostaglandin antagonists, polyphloretin phosphate and 7-oxa-13-prostynoic acid, blocked the prostaglandin E- and F-induced contractions but did not alter the ability of PGE1 to raise cAMP levels. The results suggest that interaction with adenylate cyclase is not a prerequisite for the prostaglandins to induce contractions in uterine smooth muscle. The differences in the action of epinephrine and PGE on uterine motility may reflect compartmentalization of the cAMP formed in response to these agents.
ACKNOWLEDGMENTS We are grateful to Professor H. Clauser for advice and helpful discussions throughout this work. We would like to thank Dr. J. E. Pike, Upjohn Company, Kalamazoo, who provided us with the prostaglandins; Dr. J. Fried, for the generous gift of 7-oxa-13-prostynoic acid; and Dr. B. Vargaftig, for the polyphloretin phosphate (provided to him by Dr. B. Högberg). Finally, we express our thanks to Dr. G. Vassort and Mrs. M. F. Sire for the histological preparations; to Mrs. Robichon, for technical assistance, and to Mrs. Crosnier, for typing the manuscript.
- Copyright ©, 1974, by Academic Press, Inc.