Vasopressin mediates alpha 1-adrenergic stimulation of adrenocorticotropin secretion.
In conscious rats bearing venous and cerebroventricular cannulae, central administration of the alpha 1-adrenergic agonist methoxamine stimulated the secretion of ACTH, and the effect was reduced by the alpha 1-antagonist prazosin. Methoxamine was more potent in stimulating ACTH secretion when injected icv than peripherally, suggesting that the stimulant alpha 1-adrenoceptors are located in the brain rather than in the periphery. In order to investigate the relative roles of hypothalamic CRF-41 and vasopressin as mediators of the stimulant effects of alpha 1-adrenoceptors on ACTH secretion, we examined the effects of equipotent doses of antagonists to CRF-41 and vasopressin on the ACTH responses to methoxamine. The effect of methoxamine was reduced by the vasopressin antagonist dPTyr(Me) arginine vasopressin but not by the CRF-41 antagonist alpha-helical CRF-9-41, suggesting that vasopressin is more important than CRF-41 in mediating the effects of alpha 1-adrenoceptors on ACTH secretion. However, the combination of the two antagonists caused a reduction in the ACTH response to methoxamine that was greater than that of the vasopressin antagonist alone. This suggested that CRF-41 plays some role in this response, possibly by enhancing the activity of vasopressin in a synergistic manner. These two hypothalamic peptides seem to account for most of the ACTH releasing activity of alpha 1 adrenoceptor activation.
al-Damluji
S
S
Department of Endocrinology, Medical College of St Bartholomew's Hospital, London, United Kingdom.
Thomas
R
R
White
A
A
Besser
M
M
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D014667:Vasopressins / Q000037:antagonists & inhibitors / Q000502:physiology*
D011942:Receptors, Adrenergic, alpha; D014667:Vasopressins; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D008729:Methoxamine; D011224:Prazosin