Differential role of microtubules in the control of prostaglandin E2 and beta-adrenergic stimulation of cyclic AMP accumulation in the rat myometrium.
A possible modulatory role of microtubules was investigated for the beta-adrenergic and prostaglandin E2 (PGE2)-induced cyclic AMP accumulation in the estrogen-treated rat myometrium. Colchicine, vinblastine and nocodazole, three different antitubulin drugs, enhanced cyclic AMP accumulation caused by PGE2. The effect of inhibitors was dose-(0.1-5 microM) and time-dependent, increased maximal responses without changing EC50 for PGE2, did not occur with trimethyl-colchicinic acid, which does not bind to tubulin, and was totally prevented in tissues pretreated with taxol, an agent that enhances polymerization and stabilization of microtubules. Concomitantly, colchicine reduced the rate and extent of PGE2-induced refractoriness in terms of cyclic AMP. In contrast, the antitubulin drugs failed to affect the rise in cyclic AMP evoked by isoproterenol and cholera toxin but enhanced the response to prostacyclin (PGI2), which is assumed to share common receptors with PGE2. Colchicine and vinblastine also failed to alter the ability of the beta-adrenergic agonist to provoke a cyclic AMP refractory state. Stimulations induced by all effectors were totally insensitive to cytochalasin B. The data suggest a relation between the constraints associated with the microtubules and/or membrane tubulin of the myometrium and the efficacy of PGE2 and PGI2 (but not the beta-adrenergic agonist or cholera toxin) to interact with the cyclic AMP forming system.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003078:Colchicine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003571:Cytochalasin B / Q000494:pharmacology; D015232:Dinoprostone; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008870:Microtubules / Q000502:physiology*; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D014599:Uterus / Q000378:metabolism*
D004967:Estrogens; D011458:Prostaglandins E; D003571:Cytochalasin B; D000242:Cyclic AMP; D015232:Dinoprostone; D007545:Isoproterenol; D003078:Colchicine; D015056:1-Methyl-3-isobutylxanthine