Depression of the radioprotective effect of isoproterenol on mammalian cells in vitro after desensitization of the cAMP system.

A short (5 min) incubation of cultured Chinese hamster fibroblasts with the specific beta-agonist isoproterenol (1 microM) leads to an increase in the intracellular content of cAMP and a decrease in radiosensitivity of the cells. Prolonged (up to 1 h) incubation induces a desensitization of the cAMP system to isoproterenol and causes a decrease both in the cAMP-stimulating and radioprotective effect of isoproterenol. There were no detectable changes in the beta-adrenoreceptor number or binding affinity of beta-receptors to the radiolabelled beta-antagonist dihydroalprenolol in desensitized cells; cAMP-phosphodiesterase activity was also the same as in intact cells. It is proposed that a 1 h incubation of the cells with isoproterenol induces the first step of desensitization, i.e. the functional "uncoupling' of beta-receptors from adenylate cyclase. Thus, the presence of beta-receptors in cells is not enough for the realization of the radioprotective potency of isoproterenol; an intact, non-desensitized, state of the cAMP system is obligatory.