Hypothalamic α2A-adrenoceptors stimulate growth hormone release in the rat

Abstract

Oxymetazoline, the relatively selective α 2A-adrenoceptor agonist (with more than 60-fold selectivity over the α 2B-adrenoceptor subtype), was administered into the lateral ventricle (i.c.v.) of rats and plasma growth hormone (GH) levels were measured. Oxymetazoline was more potent to release GH after i.c.v. administration than was clonidine; 0.01 μg i.c.v. oxymetazoline already caused a significant release of GH, while at least 0.1 μg clonidine had to be administered to cause a similar response. The dose-response curve was of an inverted U shape since with 10 μg of oxymetazoline the plasma GH did not rise. When oxymetazoline was injected i.c.v. to rats with somatostatin fibres to the median eminence transected by an anterolateral cut in the hypothalamus there was a significant rise in plasma GH, suggesting that oxymetazoline stimulated GHRH rather than inhibited somatostatin release. Pretreatment with CH-38083 (7,8-(methylenedioxy)-14-α-hydroxy-alloberban HCl, selective for α 2-adrenoceptors but not differentiating between α 2A and α 2B subtypes), prevented the plasma GH rise normally elicited by 1 μg i.c.v. oxymetazoline. The α 2A- and α 1-selective adrenoceptor antagonist, WB-4101 (2-(2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4-benzodioxane hydrochloride), prevented the GH rise normally induced by oxymetazoline while prazosin, the α 2B- and α 1-selective adrenoceptor antagonist, prolonged the elevation occurring in the control rats between 30 and 60 min after oxymetazoline injection. Since both prazosin and WB-4101 are α 1-adrenoceptor antagonists but differ in their action on α 2A and α 2B subtypes as well as in their action on oxymetazoline-induced GH secretion, the antagonist studies suggest that oxymetazoline stimulates GH release through activation of α 2A-adrenoceptors stimulatory to GHRH release, and not by an action through α 2B- or α 2C- or α 1-adrenoceptors. Since WB-4101 also antagonized clonidine action on GH release we also suggest that the major component may be the stimulation of the α 2A-adrenoceptors in the clonidine action on GH release.