Alpha-adrenergic stimulation by clonidine increases plasma concentrations of immunoreactive beta-endorphin in rats

Peripheral administration of the alpha-adrenergic agonist clonidine (0.5 mg/kg, sc) evoked a 2- to 3-fold rise (0.22 +/- 0.03 to 0.59 +/- 0.05 ng/ml) in plasma levels of beta-endorphin-like immunoreactivity (beta-END-LI) 15-30 min later in intact, but not hypophysectomized, rats. This rise in plasma beta-END-LI, which was dose dependent up to 0.5 mg/kg clonidine, appeared to be mediated by activation of alpha-adrenergic receptors, since pretreatment with the alpha-adrenergic antagonists yohimbine (1 mg/kg, ip), phentolamine (1, 3, or 10 mg/kg, kp), or phenoxybenzamine (2 and 10 mg/kg, ip) partially or fully blocked clonidine's effect. By contrast, the beta-adrenergic antagonist propranolol (1 and 5 mg/kg, ip) did not modify the clonidine-induced increased in plasma beta-END-LI. Given alone, the adrenergic blocking drugs were generally without effect on plasma levels of beta-END-LI. Clonidine appeared to be acting on the brain (or pituitary), since the intracerebroventricular injection of phenoxybenzamine (20 microgram) blocked the drug-induced rise in plasma beta-END-LI. These data suggest an alpha-adrenergic mechanism influences the release of pituitary beta-END in the rat.