Effect of alpha 1- and alpha 2-adrenoceptor agonists and antagonists on ACTH secretion in intact and in hypothalamic...

The effect of systemically injected alpha 1- and alpha 2-adrenoceptor agonists and antagonists on ACTH secretion was studied in rats. Epinephrine, norepinephrine, phenylephrine, clonidine, B-HT933, and B-HT920 caused a significant and dose-related increase of the ACTH concentration in the serum. The order of median effective dose (ED50) of these drugs on ACTH secretion was as follows: epinephrine not equal to norepinephrine less than B-HT920 less than clonidine less than phenylephrine much less than B-HT933. Isoproterenol, a beta-adrenoceptor agonist, had no effect on ACTH secretion. ACTH secretion induced by epinephrine or phenylephrine was significantly inhibited by alpha-adrenoceptor antagonists, phentolamine and phenoxybenzamine. However, propranolol, a beta-adrenoceptor antagonist, had no effect on ACTH secretion induced by epinephrine. Prazosin, an alpha 1-antagonist, and yohimbine, an alpha 2-antagonist, significantly blocked ACTH secretion induced by phenylephrine, an alpha 1-agonist, and B-HT933, an alpha 2-agonist, respectively. ACTH secretion induced by norepinephrine or a low dose of clonidine was inhibited by both prazosin and yohimbine. However, ACTH secretion induced by a high dose of clonidine was blocked only by prazosin. In rats with complete deafferentation of the medial basal hypothalamus (MBH), ACTH secretion induced by epinephrine, norepinephrine, and clonidine was significantly blocked, as compared with intact rats. These results suggest that both peripheral alpha 1- and alpha 2-adrenoceptors are involved in ACTH secretion induced by systemically injected adrenergic drugs in rats, and intact neural pathways entering the MBH are necessary for this ACTH releasing action.