title: Urocortin 1 reduces food intake and ghrelin secretion via CRF(2) receptors.
abstract: Although it is known that urocortin 1 (UCN) acts on both corticotropin-releasing factor receptors (CRF(1) and CRF(2)), the mechanisms underlying UCN-induced anorexia remain unclear. In contrast, ghrelin, the endogenous ligand for the growth hormone secretagogue receptor, stimulates food intake. In the present study, we examined the effects of CRF(1) and CRF(2) receptor antagonists (CRF(1)a and CRF(2)a) on ghrelin secretion and synthesis, c-fos mRNA expression in the caudal brain stem, and food intake following intracerebroventricular administration of UCN. Eight-week-old, male Sprague-Dawley rats were used after 24-h food deprivation. Acylated and des-acylated ghrelin levels were measured by enzyme-linked immunosorbent assay. The mRNA expressions of preproghrelin and c-fos were measured by real-time RT-PCR. The present study provided the following important insights into the mechanisms underlying the anorectic effects of UCN: 1) UCN increased acylated and des-acylated ghrelin levels in the gastric body and decreased their levels in the plasma; 2) UCN decreased preproghrelin mRNA levels in the gastric body; 3) UCN-induced reduction of plasma ghrelin and food intake were restored by CRF(2)a but not CRF(1)a; 4) UCN-induced increase of c-fos mRNA levels in the caudal brain stem containing the nucleus of the solitary tract (NTS) was inhibited by CRF(2)a; and 5) UCN-induced reduction of food intake was restored by exogenous ghrelin and rikkunshito, an endogenous ghrelin secretion regulator. Thus, UCN increases neuronal activation in the caudal brain stem containing NTS via CRF(2) receptors, which may be related to UCN-induced inhibition of both ghrelin secretion and food intake.
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yakabi
authors.forename: Masamichi
authors.initials: M
authors.lastname: Noguchi
authors.forename: Shino
authors.initials: S
authors.lastname: Ohno
authors.forename: Shoki
authors.initials: S
authors.lastname: Ro
authors.forename: Tsuneko
authors.initials: T
authors.lastname: Onouchi
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Ochiai
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Takabayashi
authors.forename: Kiyoshige
authors.initials: K
authors.lastname: Takayama
authors.forename: Yumi
authors.initials: Y
authors.lastname: Harada
authors.forename: Chiharu
authors.initials: C
authors.lastname: Sadakane
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Hattori
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D005744:Gastric Acid / Q000378:metabolism; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D054439:Ghrelin / Q000378:metabolism* / Q000494:pharmacology; D057967:Infusions, Intraventricular; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism / Q000502:physiology*; D055571:Secretory Pathway / Q000187:drug effects; D054832:Urocortins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C101531:CRF receptor type 2; D004365:Drugs, Chinese Herbal; D054439:Ghrelin; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C084136:liu-jun-zi-tang