title: Neuropeptide W stimulates adrenocorticotrophic hormone release via corticotrophin-releasing factor but not via arginine vasopressin.
abstract: Neuropeptide W (NPW) was isolated as an endogenous ligand for NPBWR1, an orphan G protein-coupled receptor localized in the rat brain, including the paraventricular nucleus. It has been reported that central administration of NPW stimulates corticosterone secretion in rats. We hypothesized that NPW activates the hypothalamic-pituitary-adrenal (HPA) axis via corticotrophin-releasing factor (CRF) and/or arginine vasopressin (AVP). NPW at 1 pM to 10 nM did not affect basal or ACTH-induced corticosterone release from dispersed rat adrenocortical cells, or basal and CRF-induced ACTH release from dispersed rat anterior pituitary cells. In conscious and unrestrained male rats, intravenous administration of 2.5 and 25 nmol NPW did not affect plasma ACTH levels. However, intracerebroventricular (icv) administration of 2.5 and 5.0 nmol NPW increased plasma ACTH levels in a dose-dependent manner at 15 min after stimulation (5.0 vs. 2.5 nmol NPW vs. vehicle: 1802 ± 349 vs. 1170 ± 204 vs. 151 ± 28 pg/mL, respectively, mean ± SEM). Pretreatment with astressin, a CRF receptor antagonist, inhibited the increase in plasma ACTH levels induced by icv administration of 2.5 nmol NPW at 15 min (453 ± 176 vs. 1532 ± 343 pg/mL, p<0.05) and at 30 min (564 ± 147 vs. 1214 ± 139 pg/mL, p<0.05) versus pretreatment with vehicle alone. However, pretreatment with [1-(β-mercapto-β, β-cyclopentamethylenepropionic acid), 2-(Ο-methyl)tyrosine]-arg-vasopressin, a V1a/V1b receptor antagonist, did not affect icv NPW-induced ACTH release at any time (p>0.05). In conclusion, we suggest that central NPW activates the HPA axis by activating hypothalamic CRF but not AVP.
authors.affiliation: Second Division, Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Yogo
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oki
authors.forename: Kazumi
authors.initials: K
authors.lastname: Iino
authors.forename: Miho
authors.initials: M
authors.lastname: Yamashita
authors.forename: Shoko
authors.initials: S
authors.lastname: Shibata
authors.forename: Chiga
authors.initials: C
authors.lastname: Hayashi
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Sasaki
authors.forename: Toshiko
authors.initials: T
authors.lastname: Suenaga
authors.forename: Daiichiro
authors.initials: D
authors.lastname: Nakahara
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000502:physiology*; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D004353:Drug Evaluation, Preclinical; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D006727:Hormone Antagonists; D009479:Neuropeptides; D018019:Receptors, Corticotropin-Releasing Hormone; C496874:neuropeptide W, rat; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone