Role of gaseous neurotransmitters in the hypothalamic-pituitary-adrenal axis.
Nitric oxide (NO) is an unstable gas that plays important roles in the brain in general and in neuroendocrine functions in particular. We have shown that NO exerts opposite effects within the median eminence-pituitary axis, where it inhibits ACTH responses to blood-borne signals [such as the systemic injection of proinflammatory cytokines or vasopressin (VP)], and structures protected by the blood-brain barrier, where it stimulates the synthesis of the hypothalamic peptides, corticotropin-releasing factor (CRF) and VP. As a result, when an animal is exposed to stimuli that acutely activate the paraventricular nucleus of the hypothalamus as well as the release of peptides from nerve terminals (such as mild inescapable foot shocks), the net influence of NO on the ACTH response will represent the balance between these two effects. Based on experiments conducted with rats, we propose that, in shocks of low intensity, ACTH release primarily depends, at least in the initial phase, on the interaction between NO and VP (and consequently is augmented by reagents that block NO formation); in shocks of higher intensity, the interaction between NO and the hypothalamus predominates (i.e., it is inhibited by reagents that block NO formation).
Rivier
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The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037, USA. crivier@salk.edu
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D004597:Electroshock; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D051381:Rats; D012636:Secretory Rate / Q000187:drug effects; D013312:Stress, Physiological / Q000503:physiopathology; D014667:Vasopressins / Q000494:pharmacology / Q000502:physiology
D016207:Cytokines; D004791:Enzyme Inhibitors; D014667:Vasopressins; D009569:Nitric Oxide; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019331:NG-Nitroarginine Methyl Ester