Parallel stimulation of ACTH, β-LPH + β-endorphin and α-MSH release by α-adrenergic agents in rat anterior pituitary cells in culture

Abstract

Characteristics of the α-adrenergic stimulation of ACTH, β-endorphin + β-LPH and α-MSH release were studied in rat anterior pituitary cells in primary culture. Parallel changes of ACTH, β-endorphin + β-LPH and α-MSH release were found under all stimulatory and inhibitory conditions by natural and synthetic catecholamine agonists and antagonists. (−)Epinephrine and (−)norepinephrine lead to a 8–10-fold stimulation of peptide release at ED 50 values of 20 and 90 nM, respectively. The stereoselectivity of the α-adrenergic stimulatory action on peptide release is indicated by a 100-fold higher activity of (−)- than (+)norepinephrine while (−)-epinephrine is 10 times more potent than the corresponding (+) stereoisomer. The involvement of a typical α-adrenergic mechanism in the control of release of ACTH, β-endorphin and related peptides in rat anterior pituitary gland is indicated by the following order of potency of a series of catecholaminergic agents (ED 50 values): (−)epinephrine (20 nM) > (−)norepinephrine (90 nm) > phenylephrine (400 nM) > isoproterenol (6000 nM). The stimulatory effect of (−)epinephrine or phenylephrine is completely reversed by low concentrations of the α-adrenergic antagonist phentolamine while the β-adrenergic antagonist propranolol has no effect up to 10 μM. Beside providing an easily accessible pure population of post-synaptic α-adrenergic receptors having potential applications as a model for other less accessible α-adrenergic brain systems, the present data suggest the possibility of the direct involvement of a catecholamine in the physiological control of ACTH secretion in the rat anterior pituitary gland.