부산대학교 도서관

A short (5 min) incubation of cultured Chinese hamster fibroblasts with the specific β-agonist isoproterenol (1 μm) 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 β-adrenoreceptor number or binding affinity of β-receptors to the radiolabelled β-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 β-receptors from adenylate cyclase. Thus, the presence of β-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.