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.