PMID- 11412343 OWN - NLM STAT- MEDLINE DCOM- 20010726 LR - 20190921 IS - 0953-8194 (Print) IS - 0953-8194 (Linking) VI - 13 IP - 6 DP - 2001 Jun TI - The central effects of orexin-A in the hypothalamic-pituitary-adrenal axis in vivo and in vitro in male rats. PG - 561-6 AB - Orexin-A is synthesized in the posterolateral hypothalamus and immunoreactive fibres project to many central nervous system structures, including the paraventricular nucleus, which is rich in corticotropin releasing factor (CRF) neurones and neuropeptide Y (NPY) innervation. We investigated the central effects of orexin-A on the hypothalamic-pituitary-adrenal (HPA) axis by measuring plasma concentrations of corticosterone and adrenocorticotropic hormone (ACTH) in vivo. We explored the potential neuropeptide pathways involved by investigating the effects of orexin-A on CRF, NPY, arginine vasopressin (AVP) and noradrenaline release from hypothalamic explants in vitro. Intracerebroventricular (i.c.v.) injection of orexin-A (3 nmol) in male rats stimulated increases in plasma concentrations of corticosterone between 10 and 40 min after injection, and of plasma ACTH at 20 and 90 min after injection. Orexin-A significantly stimulated CRF and NPY release from hypothalamic explants in vitro. Orexin-A did not stimulate CRF release in the presence of the selective NPY Y1 receptor antagonist, BIBP3226. BIBP3226 alone did not alter CRF release from hypothalamic explants. Orexin-A had no effect in vitro on the release of other neuropeptides, AVP and noradrenaline, involved in the central regulation of the HPA axis. These results suggest that orexin-A is involved in activation of the HPA axis, and that these effects could be mediated via the release of NPY. FAU - Russell, S H AU - Russell SH AD - ICSM Endocrine Unit, ICSM, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK. FAU - Small, C J AU - Small CJ FAU - Dakin, C L AU - Dakin CL FAU - Abbott, C R AU - Abbott CR FAU - Morgan, D G AU - Morgan DG FAU - Ghatei, M A AU - Ghatei MA FAU - Bloom, S R AU - Bloom SR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neuroendocrinol JT - Journal of neuroendocrinology JID - 8913461 RN - 0 (BIBP 3226) RN - 0 (Carrier Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Neuropeptide Y) RN - 0 (Neuropeptides) RN - 0 (Orexins) RN - 113-79-1 (Arginine Vasopressin) RN - 9002-60-2 (Adrenocorticotropic Hormone) RN - 9015-71-8 (Corticotropin-Releasing Hormone) RN - 94ZLA3W45F (Arginine) RN - W980KJ009P (Corticosterone) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - Adrenal Glands/*drug effects MH - Adrenocorticotropic Hormone/blood MH - Animals MH - Arginine/*analogs & derivatives/pharmacology MH - Arginine Vasopressin/metabolism MH - Carrier Proteins/administration & dosage/*pharmacology MH - Corticosterone/blood MH - Corticotropin-Releasing Hormone/metabolism MH - Culture Techniques MH - Hypothalamus/*drug effects/metabolism MH - Injections, Intraventricular MH - *Intracellular Signaling Peptides and Proteins MH - Kinetics MH - Male MH - Neuropeptide Y/metabolism MH - Neuropeptides/administration & dosage/*pharmacology MH - Norepinephrine/metabolism MH - Orexins MH - Pituitary Gland/*drug effects MH - Rats MH - Rats, Wistar EDAT- 2001/06/20 10:00 MHDA- 2001/07/28 10:01 CRDT- 2001/06/20 10:00 PHST- 2001/06/20 10:00 [pubmed] PHST- 2001/07/28 10:01 [medline] PHST- 2001/06/20 10:00 [entrez] AID - jne672 [pii] AID - 10.1046/j.1365-2826.2001.00672.x [doi] PST - ppublish SO - J Neuroendocrinol. 2001 Jun;13(6):561-6. doi: 10.1046/j.1365-2826.2001.00672.x.