Orexin actions in hypothalamic paraventricular nucleus: physiological consequences and cellular correlates.
Orexinergic neurons originating in the perifornical, lateral hypothalamus project to numerous brain sites including neuroendocrine centers known to be important in the physiologic response to stress. Those projections suggest an action of endogenous orexin on adrenocorticotropin (ACTH) release, either by neuromodulatory effects in the paraventricular nucleus (PVN), or by neuroendocrine actions in the pituitary gland following release into the median eminence. We sought to determine if exogenously applied orexin A might act in the brain to alter ACTH release and to determine if a site of action in the hypothalamic paraventricular nucleus could be identified. Cerebroventricular administration of orexin A in conscious male rats resulted in a dose-related elevation in circulating ACTH levels. At 30 min post-infusion, ACTH levels were elevated 2.5-fold by the low dose of orexin A (0.3 nmol), 5.7-fold by the middle dose tested (1.0 nmol), and 7.5-fold by the highest dose tested (3.0 nmol). Pretreatment with a CRH-antagonist (i.v.) blocked the ability of i.c.v. administered orexin A to activate the hypothalamo-pituitary-adrenal (HPA) axis. Bath application of orexin A in hypothalamic slice preparations resulted in depolarizations (8.0+/-0.6 mV), accompanied by increases in spike frequency in identified magno- and parvocellular neurons in the PVN. Our data suggest a potential role for endogenous orexin in the hypothalamic regulation of stress hormone secretion.
Samson
Willis K
WK
Department of Pharmacological and Physiological Sciences, Saint Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104, USA. samsonwk@slu.edu
Taylor
Meghan M
MM
Follwell
Matthew
M
Ferguson
Alastair V
AV
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D022081:Cell Surface Extensions / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007276:Injections, Intraventricular / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology*; D000068797:Orexins; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D010446:Peptide Fragments; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41)