Norepinephrine-sensitive adenylate cyclase system in rat brain: role of adrenal corticosteroids

Two weeks after bilateral adrenalectomy, the responsiveness of the norepinephrine (NE)-sensitive adenylate cyclase system in the rat frontal cortex was increased. This effect was restricted to the non-beta-component of the system as no change was observed in the cyclic AMP response elicited by isoproterenol after bilateral adrenalectomy, thus indicating that subpopulations of cortical NE receptor systems are under separate endocrine control. The effect of adrenalectomy on the NE-sensitive adenylate cyclase system could be completely reversed by administering corticosterone for 3 days. No changes in the cyclic AMP response to NE were observed 2 weeks after bilateral medullectomy. Furthermore, an increase in the responsiveness of the system was also observed 2 weeks after hypophysectomy. These results suggest that the effects observed in the NE-sensitive adenylate cyclase system after adrenalectomy are mediated by the loss of adrenal corticosteroids. Adrenalectomy did not alter the activities of either adenylate cyclase or phosphodiesterase. No apparent changes were observed in the maximum binding or dissociation constant values of either beta or alpha adrenoceptors as assessed with [3H]alprenolol, [3H]WB-4101 and [ [3H]clonidine. Furthermore, the effects of adrenalectomy cannot be accounted for by a shift in the diurnal variation of the system as the cyclic AMP response to NE in tissue from adrenalectomized animals was higher than that in tissue from shamoperated rats throughout a 24-hr period.