Presynaptic alpha 2 -adrenergic stimulation leads to growth hormone release in the dog.
In previous studies we have shown that the alpha 2 -adrenergic receptor agonist clonidine (CLON) releases growth hormone (GH) in conscious dogs, an effect abolished by the selective alpha 2-receptor antagonist yohimbine (YOH) and by reserpine, but not by the alpha 1-receptor antagonist prazosin (1). In the present work intravenous (iv) administration of CLON in conscious dogs evoked a dose-related rise in plasma GH at doses of 2-8 /micrograms/Kg, but not at 16 and 32 /micrograms/Kg. Acute pretreatment with the selective inhibitor of norepinephrine (NE) synthesis, DU-18288, or with a potent antagonist of presynaptic alpha 2-receptors, mianserin abolished the GH rise induced by CLON (4 /micrograms/Kg iv). In contrast, a 10-day-pretreatment with YOH greatly enhanced the GH-releasing effect of CLON (2 /micrograms/Kg iv). In all these data indicate that in the dog: 1) CLON induces GH release via activation of alpha 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/micrograms/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 alpha 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.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002974:Clemastine / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D008803:Mianserin / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D014230:Triazoles; D008711:Metergoline; D008803:Mianserin; D015016:Yohimbine; C040439:N,N-dimethyl-N'-1H-1,2,4-triazol-3-yl-thiourea; D013006:Growth Hormone; D002974:Clemastine; D003000:Clonidine