FACTORS FROM THE PARAVENTRICULAR NUCLEUS MEDIATE INHIBITORY EFFECT OFALPHA-2-ADRENERGIC DRUGS ON ACTH-SECRETION

The controversy about putative stimulatory and inhibitory functions of catecholamines in regulation of ACTH secretion has been recently shif ted towards a consensus that during stress catecholamines stimulate co rticotropin-releasing factor (CRF-41) containing neurons through alpha 1-adrenoreceptors, while inhibiting their own secretion acting on pres ynaPtiC alpha2-receptors. In this study the effect of the alpha2-agoni st clonidine and the antagonist CH-38083 was studied on exogenous CRF- 41/AVP-induced ACTH secretion in rats with/without paraventricular nuc leus lesion. Clonidine (30 mug/kg) attenuated CRF-41/AVP (1 pmol/10 pm ol)-induced ACTH secretion in sham-operated rats, but was ineffective in reducing CRF-41/AVP-induced ACTH secretion in rats with paraventric ular nucleus lesion. In sham-operated rats, alpha2-receptor antagonist CH-38083 slightly elevated the basal, and significantly potentiated t he CRF-41/AVP-induced ACTH secretion, while it had no effect on the hy pophyseotropic cocktail-induced ACTH response in paraventricular-lesio ned rats. Neither the agonist nor the antagonist affected CRF-41/AVP-i nduced ACTH release from pituitary fragments in vitro. These results s uggest that in response to activation of alpha2-adrenoreceptors a cort icotropin release-inhibiting substance is released from the paraventri cular nucleus.