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Am J Physiol Regul Integr Comp Physiol 281: R1401-R1410, 2001;
0363-6119/01 $5.00
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Vol. 281, Issue 5, R1401-R1410, November 2001

Peripheral urocortin inhibits gastric emptying and food intake in mice: differential role of CRF receptor 2

Lixin Wang1, Vicente Martínez1,2, Jean E. Rivier3, and Yvette Taché1

1 Center for Ulcer Research and Education: Digestive Diseases Research Center, Veterans Affairs Greater Los Angeles Healthcare System, Department of Medicine, Division of Digestive Diseases and Brain Research Institute, University of California at Los Angeles, Los Angeles 90073; 3 Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037; and 2 Cardenal Herrera University, Department of Basic Biomedical Sciences, 46113 Moncada, Valencia, Spain

Intraperitoneal urocortin inhibits gastric emptying and food intake in mice. We investigated corticotropin-releasing factor receptor (CRF-R) subtypes involved in intraperitoneal urocortin actions using selective CRF-R antagonists. Gastric emptying was measured 2 h after a chow meal, and food intake was measured hourly after an 18-h fast in mice. Urocortin (3 µg/kg ip) inhibited gastric emptying by 88%. The CRF-R1/CRF-R2 antagonist astressin B (30 µg/kg ip) and the selective CRF-R2 antagonist antisauvagine-30 (100 µg/kg ip) completely antagonized urocortin action, whereas the selective CRF-R1 antagonist CP-154,526 (10 mg/kg ip) had no effect. Urocortin (1-10 µg/kg ip) dose dependently decreased the 2-h cumulative food intake by 30-62%. Urocortin (3 µg/kg)-induced hypophagia was completely antagonized by astressin B (30 µg/kg ip) and partially (35 and 31%) by antisauvagine-30 (100 or 200 µg/kg ip). The CRF-R1 antagonists CP-154,526 or DMP904 (10 mg/kg ip) had no effect. Capsaicin did not alter urocortin-inhibitory actions while blocking the satiety effect of intraperitoneal CCK. These data indicate that intraperitoneal urocortin-induced decrease in feeding is only partly mediated by CRF-R2, whereas urocortin action to delay gastric emptying of a meal involves primarily CRF-R2.

antisauvagine-30; astressin B; capsaicin; cholecystokinin; CP-154,526; DMP904; corticotropin-releasing factor


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