title: Intracerebroventricular urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via CRF receptor 2 in rats.
abstract: OBJECTIVE
  Urocortin 3 is a key neuromodulator in the regulation of stress, anxiety, food intake, gut motility, and energy homeostasis, while ghrelin elicits feeding behavior and enhances gastric emptying, adiposity, and positive energy balance. However, the interplays between urocortin 3 and ghrelin on food intake and gastric emptying remain uninvestigated.
  
  
  METHODS
  We examined the differential effects of centralO-n-octanoylated ghrelin, des-Gln14-ghrelin, and urocortin 3 on food intake, as well as on charcoal nonnutrient semiliquid gastric emptying in conscious rats that were chronically implanted with intracerebroventricular (ICV) catheters. The functional importance of corticotropin-releasing factor (CRF) receptor 2 in urocortin 3-induced responses was examined by ICV injection of the selective CRF receptor 2 antagonist, astressin2-B.
  
  
  RESULTS
  ICV infusion of urocortin 3 opposed central acyl ghrelin-elicited hyperphagia via CRF receptor 2 in satiated rats. ICV injection ofO-n-octanoylated ghrelin and des-Gln14-ghrelin were equally potent in accelerating gastric emptying in fasted rats, whereas ICV administration of urocortin 3 delayed gastric emptying. In addition, ICV infusion of urocortin 3 counteracted central acyl ghrelin-induced gastroprokinetic effects via CRF receptor 2 pathway.
  
  
  CONCLUSIONS
  ICV-infused urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via CRF receptor 2 in rats. Our results clearly showed that enhancing ghrelin and blocking CRF receptor 2 signaling in the brain accelerated gastric emptying, which provided important clues for a new therapeutic avenue in ameliorating anorexia and gastric ileus found in various chronic wasting disorders.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Cheng-Hsin General Hospital.
authors.forename: Chun
authors.initials: C
authors.lastname: Yeh
authors.affiliation: Department of Pathology, Mackay Memorial Hospital.
authors.forename: Ching-Heng
authors.initials: CH
authors.lastname: Ting
authors.affiliation: Institute of Physiology.
authors.forename: Ming-Luen
authors.initials: ML
authors.lastname: Doong
authors.affiliation: Institute of Pharmacology, National Yang-Ming University School of Medicine; Department of Medical Research, Taipei Veterans General Hospital.
authors.forename: Chin-Wen
authors.initials: CW
authors.lastname: Chi
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Cheng-Hsin General Hospital.
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Lee
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital; Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei; Taiwan Association for the Study of Small Intestinal Diseases, Guishan, Taiwan.
authors.forename: Chih-Yen
authors.initials: CY
authors.lastname: Chen
mesh_terms: D000818:Animals; D057785:Catheters; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage; D004435:Eating / Q000187:drug effects*; D005746:Gastric Emptying / Q000187:drug effects*; D054439:Ghrelin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D006963:Hyperphagia / Q000139:chemically induced / Q000378:metabolism; D057967:Infusions, Intraventricular; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D054832:Urocortins / Q000008:administration & dosage*
chemical_list: C101531:CRF receptor type 2; D054439:Ghrelin; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C104416:astressin; D003346:Corticotropin-Releasing Hormone
keywords: corticotropin-releasing factor receptor; des-Gln14-ghrelin; food intake; gastric emptying; intracerebroventricular; urocortin 3