The central effects of orexin-A in the hypothalamic-pituitary-adrenal axis in vivo and in vitro in male rats.
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.
Russell
S H
SH
ICSM Endocrine Unit, ICSM, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK.
Small
C J
CJ
Dakin
C L
CL
Abbott
C R
CR
Morgan
D G
DG
Ghatei
M A
MA
Bloom
S R
SR
D000311:Adrenal Glands / Q000187:drug effects*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000378:metabolism; D002352:Carrier Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D046508:Culture Techniques; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D000068797:Orexins; D010902:Pituitary Gland / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
C092926:BIBP 3226; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D000068797:Orexins; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D001120:Arginine; D003345:Corticosterone; D009638:Norepinephrine