Neuropeptide W stimulates adrenocorticotrophic hormone release via corticotrophin-releasing factor but not via arginine vasopressin

• Published in: Endocrine Journal 2012, Vol.59(7), pp.547-554
• Main Authors: Yogo, Kosuke, Oki, Yutaka, Iino, Kazumi, Yamashita, Miho, Shibata, Shoko, Hayashi, Chiga, Sasaki, Shigekazu, Suenaga, Toshiko, Nakahara, Daiichiro, Nakamura, Hirotoshi
• Format: Article
• Language: English
• Subjects: ACTH; Adrenocorticotropic Hormone - blood; Adrenocorticotropic Hormone - metabolism; Animals; Antidiuretic Hormone Receptor Antagonists; Arginine vasopressin; Arginine Vasopressin - physiology; Cells, Cultured; Corticosterone - metabolism; Corticotropin-releasing factor; Corticotropin-Releasing Hormone - physiology; Drug Evaluation, Preclinical; Hormone Antagonists - administration & dosage; Hormone Antagonists - pharmacology; Injections, Intravenous; Male; Neuropeptide W; Neuropeptides - administration & dosage; Neuropeptides - pharmacology; NPBWR1; Pituitary Gland, Anterior - cytology; Pituitary Gland, Anterior - drug effects; Pituitary Gland, Anterior - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Corticotropin-Releasing Hormone - antagonists & inhibitors; Signal Transduction - drug effects; Signal Transduction - physiology; Up-Regulation - drug effects
• ISSN: 0918-8959; 1348-4540
• DOI: 10.1507/endocrj.EJ11-0221

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