Cyclic AMP binding to intracellular receptor proteins in rat myometrium. Effect of epinephrine and prostaglandin E1.
In estrogen-pretreated rat myometrium, the relaxing effect exerted by theophylline or epinephrine has been correlated with their ability to raise cyclic AMP levels (Vesin and Harbon, 1974). The present study demonstrates that such a correlation can be quantitatively extended to the degree of saturation of intracellular cyclic AMP receptors. The rise in cyclic AMP induced by theophylline and/or epinephrine in intact myometrial strips was accompanied by a decrease in the ability of the corresponding extracts to bind exogenous 3H-labeled cyclic AMP. Total intracellular cyclic AMP binding sites were not modified and averaged a value of 0.22 muM. Accurate estimation of intracellular receptor-cyclic AMP complex has been correlated with the corresponding level of cyclic AMP in the tissue, the apparent intracellular Kd for cyclic AMP has been evaluated at 450 nm. Stimulation of myometrial strips with prostaglandin E1 (PGE1) which has been shown previously to induce contractions, although elevating cyclic AMP levels, was accompanied by a parallel increase in the saturation of the endogenous receptor, in an identical manner to that found with epinephrine or theophylline. The postulated hypothesis for a compartmentalization of cyclic AMP, or an interference of PGE1 with the intracellular cyclic AMP binding equilibrium has not been verified. The cyclic AMP system cannot be considered as the exclusive mechanism regulating uterine relaxation.
D000818:Animals; D001667:Binding, Competitive; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D007700:Kinetics; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D011953:Receptors, Cyclic AMP / Q000187:drug effects / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology; D014599:Uterus / Q000378:metabolism*
D011458:Prostaglandins E; D011953:Receptors, Cyclic AMP; D004958:Estradiol; D003994:Bucladesine; D013806:Theophylline; D000242:Cyclic AMP; D004837:Epinephrine