Alpha 1-adrenergic stimulation of ACTH secretion in vivo in the rat.
The alpha-adrenergic agonist phenylephrine (100 micrograms, i.v.) causes a rapid 5- to 10-fold elevation of plasma ACTH levels 5 min after its administration in adult ovariectomized rats, the concentration of the hormone remaining elevated up to at least 2h. Epinephrine (10 micrograms) causes also a rapid but shorter-lived stimulation of ACTH secretion. While having no effect alone under basal conditions (conscious freely-moving animals), the highly specific alpha 1-adrenergic antagonist prazosin (0.25 micrograms) almost completely reverses the stimulatory effect of phenylephrine. Pretreatment with dexamethasone inhibits basal plasma ACTH levels by 70% and almost completely prevents the stimulatory effect of phenylephrine on this parameter. Plasma levels of alpha-MSH, on the other hand, are only stimulated 1-fold above control 5 min after the administration of phenylephrine and are insensitive to corticosteroid treatment. Based on the specificity of action of prazosin on postsynaptic alpha 1-adrenergic receptors and of dexamethasone on the anterior lobe of the pituitary gland, the present data indicate that phenylephrine is a potent stimulator of ACTH secretion by a direct action on an alpha 1-adrenergic receptor in corticotrophs of the adenohypophysis. They also support the suggestion that epinephrine and/or norepinephrine could be involved as physiological corticotropin-releasing factor(s).
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D010656:Phenylephrine / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D004837:Epinephrine