Homologous desensitization of rat heart cells to beta-adrenergic stimulation and the absence of alpha-adrenergic or prostaglandin E1 effects.
Epinephrine is shown to stimulate heart cell beating by both alpha- and beta-adrenergic mechanisms. The beta-adrenergic effect undergoes desensitization in one to two minutes after beta-agonist addition. A beta-antagonist did not cause desensitization. The desensitization response is quantitatively related to the concentration of cAMP produced in the cells. The alpha-adrenergic component of epinephrine action does not undergo desensitization nor does it have effects on the beta-adrenergic stimulation of cell beating or cAMP production. Other alpha-agonists and antagonists also have no effect on cAMP production. Prostaglandin E1 increased cellular cAMP by a mechanism that was additive with the beta-adrenergic mechanism. Both prostaglandin E1 and beta-agonists caused phosphorylation of both glycogen phosphorylase and glycogen synthase. Prostaglandin E1 did not desensitize the cells to beta-adrenergic stimulation of cAMP. The data show that heart cells undergo a rapid homologous desensitization to beta-agonists when treated with epinephrine or isoproterenol. The desensitization is quantitatively related to the cellular cAMP concentration, but cAMP produced by another mechanism does not desensitize the cells. No alpha-adrenergic effects on the beta-induced desensitization were observed.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000527:Alprostadil; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004351:Drug Resistance; D004837:Epinephrine / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D011458:Prostaglandins E; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D000527:Alprostadil; D004837:Epinephrine