Alpha-adrenergic stimulation of corticotropin secretion by a specific central mechanism in man.
In a double-blind study in normal subjects, methoxamine, a highly selective agonist at alpha-1-adrenoceptors, significantly increased circulating ACTH and cortisol. The stimulant effect of methoxamine on cortisol secretion was dose dependent in the range 3.5-7 micrograms/kg/min, was abolished by concomitant administration of the strong alpha-1-adrenergic (and weak H1) antagonist thymoxamine but unaffected by the antihistamine, chlorpheniramine. In order to test whether the action of methoxamine on ACTH secretion was exerted centrally or peripherally, the effects of norepinephrine (NE), an alpha-1-agonist that does not cross the blood-brain barrier, were studied. Doses of NE (1-12 micrograms/min) that increased systolic blood pressure by amounts similar to the changes produced by methoxamine, did not result in any rise in plasma cortisol in normal subjects. The effect of methoxamine, which is more lipid soluble than NE, on plasma ACTH and cortisol, appears to be exerted on the CNS and not at the pituitary or via nonspecific peripheral mechanisms. In addition to its water solubility, NE differs from methoxamine in its beta-1-, beta-2- and alpha-2-agonist actions. However, prenalterol (2 mg) and salbutamol (250 micrograms), respectively beta-1- and beta-2-adrenergic agonist drugs, had no effect on the secretion of ACTH or cortisol and the alpha-2-antagonist yohimbine in an effective dose did not unmask a stimulant effect of intravenous NE on plasma cortisol. At high infusion rates, NE significantly inhibited cortisol secretion. Stimulation of central alpha-1-adrenergic mechanisms results in secretion of ACTH in man, presumably by increased release of a corticotropin-releasing factor.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D000420:Albuterol / Q000494:pharmacology; D002744:Chlorpheniramine / Q000494:pharmacology; D004311:Double-Blind Method; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011294:Prenalterol / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D002744:Chlorpheniramine; D000324:Adrenocorticotropic Hormone; D008729:Methoxamine; D011294:Prenalterol; D000420:Albuterol; D006854:Hydrocortisone; D009638:Norepinephrine