Adrenocorticotropin, prolactin and beta-endorphin stimulatory actions of alpha-2-adrenoceptor antagonists.
We studied the effect of glucocorticoid pretreatment, mediobasal hypothalamus lesion (MBHL) and the interaction between clonidine and yohimbine in male Wistar rats to elucidate the sites and/or mechanisms of endocrine actions of alpha 2-antagonists. The pretreatment of 1 mg/kg s.c. dexamethasone for 4 days effectively prevented the stimulatory effect of alpha 2-antagonists yohimbine (5 mg/kg i.p.) and CH-38083 (1 mg/kg i.p.) on adrenocorticotropin (ACTH) secretion, while the action of these antagonists on prolactin (PRL) and beta-endorphin (beta E) remained unchanged. The central (i.c.v.) pretreatment of 5 micrograms/rat clonidine failed to antagonize the prolactin (PRL) and beta E releasing effect of yohimbine. However, it inhibited the yohimbine-induced ACTH secretion. MBHL resulted in a significant enhancement in basal plasma PRL and beta-endorphin (beta E) levels. But basal plasma ACTH levels have not been changed. Yohimbine failed to stimulate ACTH secretion in MBH-lesions rats, while PRL and beta E response to the yohimbine was maintained in these animals. This study confirms that the alpha 2-antagonists stimulate ACTH secretion by a corticosteroid-sensitive mechanism which is located centrally. In contrast, alpha 2-antagonists affect PRL and beta E secretion via a corticosteroid-insensitive mechanism located at the periphery, possible within the pituitary gland.
Kiem
D T
DT
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
Barna
I
I
Koenig
J I
JI
Makara
G B
GB
D058669:Adrenergic alpha-2 Receptor Antagonists; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D007033:Hypothalamus, Middle / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D015016:Yohimbine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001615:beta-Endorphin / Q000378:metabolism*
D058669:Adrenergic alpha-2 Receptor Antagonists; D015016:Yohimbine; D001615:beta-Endorphin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D003000:Clonidine