Factors from the paraventricular nucleus mediate inhibitory effect of alpha-2-adrenergic drugs on ACTH secretion.
The controversy about putative stimulatory and inhibitory functions of catecholamines in regulation of ACTH secretion has been recently shifted towards a consensus that during stress catecholamines stimulate corticotropin-releasing factor (CRF-41) containing neurons through alpha 1-adrenoreceptors, while inhibiting their own secretion acting on presynaptic alpha 2-receptors. In this study the effect of the alpha 2-agonist clonidine and the antagonist CH-38083 was studied on exogenous CRF-41/AVP-induced ACTH secretion in rats with/without paraventricular nucleus lesion. Clonidine (30 micrograms/kg) attenuated CRF-41/AVP (1 pmol/10 pmol)-induced ACTH secretion in sham-operated rats, but was ineffective in reducing CRF-41/AVP-induced ACTH secretion in rats with paraventricular nucleus lesion. In sham-operated rats, alpha 2-receptor antagonist CH-38083 slightly elevated the basal, and significantly potentiated the CRF-41/AVP-induced ACTH secretion, while it had no effect on the hypophyseotropic cocktail-induced ACTH response in paraventricular-lesioned rats. Neither the agonist nor the antagonist affected CRF-41/AVP-induced ACTH release from pituitary fragments in vitro. These results suggest that in response to activation of alpha 2-adrenoreceptors a corticotropin release-inhibiting substance is released from the paraventricular nucleus.
Laboratory of Neuroendocrinology, Institute of Experimental Medicine, Budapest, Hungary.
K J
KJ
Kovács
G B
GB
Makara
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology
D011942:Receptors, Adrenergic, alpha; D001599:Berberine; C048886:7,8-(methylenedioxy)-14-hydroxyberbane; D000324:Adrenocorticotropic Hormone; D003000:Clonidine