Participation of alpha 1-adrenergic receptors in the secretion of hypothalamic corticotropin-releasing hormone during stress.
The role of alpha 1-adrenergic receptors in the secretion of corticotropin-releasing hormone (CRH) during stress was studied by immunohistochemical analysis of the CRH content of the median eminence (ME) after intracerebroventricular (icv) administration of the alpha 1-adrenergic agonist, methoxamine, or the antagonist, prazosin, in rats pretreated with colchicine. Immunohistochemical staining was performed by the peroxidase technique on 40 microns free-floating sections using a polyclonal antibody specific for CRH. In the first experimental model, rats were implanted with icv cannulae and adapted to the experimental conditions by daily handling and icv injection of artificial CSF. Colchicine (75 micrograms) was administered through the cannulae 6 h before the experiment, conditions in which axonal transport was blocked with little change in basal immunostaining. Two hours after immobilization stress or a single injection of methoxamine (100 micrograms, icv), there was a marked decrease in CRH immunoreactivity throughout the ME, reflecting release of the neuropeptide into the portal circulation. The decrease in CRH immunostaining following immobilization was largely prevented by icv injection of the alpha 1-adrenergic antagonist, prazosin. In the second experimental model, rats were sacrificed 48 h after icv colchicine injection, conditions in which colchicine acts as a stressor and causes marked depletion of irCRH from the ME. This chronic effect of colchicine was also partially prevented by administration of prazosin, 400-ng injection 5 min prior to colchicine, followed by a continuous icv mini-pump infusion of prazosin, indicating that alpha 1-adrenergic stimulation contributes to the action of colchicine.(ABSTRACT TRUNCATED AT 250 WORDS)
Kiss
A
A
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, NIH, Bethesda, Md 20892.
Aguilera
G
G
D000818:Animals; D003078:Colchicine / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism; D008729:Methoxamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000503:physiopathology*
D011942:Receptors, Adrenergic, alpha; D003346:Corticotropin-Releasing Hormone; D008729:Methoxamine; D003078:Colchicine; D011224:Prazosin