Presynaptic α 2-adrenergic stimulation leads to growth hormone release in the dog

Abstract

In previous studies we have shown that the α 2-adrenergic receptor agonist clonidine (CLON) releases growth hormone (GH) in conscious dogs, an effect abolished by the selective α 2-receptor antagonist yohimbine (YOH) and by reserpine, but not by the α 1-receptor antagonist prazosin (1). In the present work intravenous (iv) administration of CLON in concious dogs evoked a dose-related rise in plasma GH at doses of 2–8 ug/Kg, but not at 16 and 32 ug/Kg. Acute pretreatment with the selective inhibitor of norepinephrine (NE) synthesis, DU-18288, or with a potent antagonist of presynaptic α 2-receptors, mianserin abolished the GH rise induced by CLON (4 ug/Kg iv). In contrast, a 10-day-pretreatment with YOH greatly enhanced the GH-releasing effect of CLON (2 ug/Kg iv). In all these data indicate that in the dog: 1) CLON induces GH release via activation of α 2-adrenergic receptors; 2) these receptors are likely located on presynaptic sites [experiments with reserpine (1), DU-18288, mianserin, dose-response curve with CLON 2–32 ug/Kg iv] ; 3) the adrenergic receptors involved in GH release exhibit supersensitivity upon (YOH-induced) chronic pharmacologic denervation. In view of the inhibitory action of presynaptic α 2-adrenergic receptors (autoreceptors) on NE function, it may be envisioned that in the dog noradrenergic activation is inhibitory and not stimulatory to GH release.