title: Role of specific adrenergic receptors in mediating the adrenocorticotropic hormone response to increased nitric oxide levels.
abstract: We investigated the role played by catecholamine-dependent pathways in modulating the ability of the nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1) to release adrenocorticotropic hormone (ACTH) following its intracerebroventricular (i.c.v.) or intravenous (i.v.) injection. We first showed that the nonspecific adrenergic agonist noradrenaline, the alpha- or beta-adrenergic agonists phenylephrine or dobutamine, or the noradrenergic uptake inhibitor desipramine, all significantly stimulated ACTH secretion by freely moving, nonanaesthetized rats. We then observed that destruction of noradrenergic nerve endings with the neurotoxin 6-hydroxydopamine, respectively abolished and significantly decreased the ACTH response to the i.c.v. or i.v. administration of SIN-1. Finally, we sought to identify the type of adrenergic receptor(s) mediating the influence of catecholamines. beta-Adrenergic receptors did not appear to be involved in the stimulatory effect of SIN-1 regardless of its route of injection. By contrast, alpha 2-adrenergic receptors played an important role in the ACTH response to i.v. or i.c.v. administered SIN-1. Collectively, these results indicate that while hypothalamic alpha 1- and beta-adrenergic receptors are important for hypothalamic-pituitary-adrenal (HPA) axis activity, only alpha 2-adrenergic receptors are involved in modulating the ability of NO to release ACTH. Our laboratory and others have previously reported that NO increased hypothalamic noradrenaline levels, while conversely noradrenaline up-regulated levels of NO synthase, the enzyme responsible for NO formation; and that injection of corticotropin-releasing factor into the brain ventricles releases catecholamines and stimulates NO formation. Taken together with these observations, our results point to complex functional relationships between NO, catecholamines and the HPA axis.
authors.affiliation: The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, CA 92037, USA.
authors.forename: D O
authors.initials: DO
authors.lastname: Seo
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Rivier
mesh_terms: D000311:Adrenal Glands / Q000502:physiology; D000322:Adrenergic Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology; D007031:Hypothalamus / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010902:Pituitary Gland / Q000502:physiology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000502:physiology*
chemical_list: D000322:Adrenergic Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D020030:Nitric Oxide Donors; D011941:Receptors, Adrenergic; D010656:Phenylephrine; D009569:Nitric Oxide; D004280:Dobutamine; C002385:linsidomine; D000324:Adrenocorticotropic Hormone; D011433:Propranolol; D008981:Molsidomine; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin