Characteristics of the α-Adrenergic Stimulation of Adrenocorticotropin Secretion in Rat Anterior Pituitary Cells

Abstract

Specificity of the a-adrenergic control of ACTH secretion was studied in rat anterior pituitary cells in primary culture. The α-adrenergic specificity of ACTH secretion is demonstrated by the following order of potency of catecholaminergic agents: epinephrine (20 nM) > norepinephrine (30 nM) » isoproterenol = doparnine (10μM). While epinephrine and norepinephrine lead to a 7- to 10-fold stimulation of ACTH secretion, clonidine and phenylephrine act as partial agonists and cause a 3- to 4-fold increase of ACTH release. Paraaminoclonidine and methoxamine have no significant effect up to 10 μM. α-Adrenergic antagonists inhibit epinephrine-induced ACTH release in the following order of potency: prazosin > WB-4101 » yohimbine, with K_a values of 0.06, 0.4, and 70 nM, respectively, thus indicating that the α-adrenergic receptor controlling ACTH secretion is of the α₁ type. Dihydroergocornine and dihydroergocryptine, two ergot derivatives, show a-adrenergic antagonistic activity at low K_d values of 0.8 and 1.5 nM, respectively. The serotonergic antagonists cyproheptadine and methysergide can also act as antagonists on the pituitary α-adrenergic receptor. The dopamine antagonists chlorpromazine, haloperidol, (+)butaclamol, and spiroperidol are also potent α-adrenergic antagonists. These data demonstrate that ACTH secretion from rat anterior pituitary cells is under specific α₁-adrenergic control. The high degree of sensitivity of the α-adrenergic mechanisms stimulating ACTH secretion in rat corticotrophs suggests that epinephrine and/or norepinephrine of hypothalamic and/or peripheral origin are involved as physiological corticotropin-releasing factors. Moreover, it is hoped that the availability of a pure population of postsynaptic α₁-adrenergic receptors controlling ACTH secretion could be used as a model for other less accessible α-adrenergic systems.