Endogenous cholecystokinin reduces food intake and increases Fos-like immunoreactivity in the dorsal vagal complex but not in the myenteric plexus by CCK1 receptor in the adult rat

1 Gastroenterology Laboratory, Department of Biomedical Sciences, College of Veterinary Medicine, Tuskegee University, Tuskegee, Alabama; 2 Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas; and 3 CURE: Digestive Diseases Research Center, Veterans Administration Greater Los Angeles Healthcare System, and Digestive Diseases Division, School of Medicine, University of California, Los Angeles California Submitted 12 July 2006 ; accepted in final form 30 October 2006 We hypothesized that endogenous CCK reduces food intake by activating the dorsal vagal complex (DVC) and the myenteric neurons of the gut. To test this hypothesis, adult rats were given camostat mesilate; a nonnutrient releaser of endogenous CCK, by orogastric gavage, and Fos-like immunoreactivity (Fos-LI) was quantified in the DVC and the myenteric plexus. The results for endogenous CCK were compared with those for exogenous CCK-8. Exogenous CCK-8 reduced food intake and stimulated Fos-LI in the DVC and in myenteric neurons of the duodenum and jejunum. In comparison, endogenous CCK reduced food intake and increased DVC Fos-LI but did not increase Fos-LI in the myenteric plexus. Similar to CCK-8, devazepide, a specific CCK 1 receptor antagonist, and not L365,260, a specific CCK 2 receptor antagonist, attenuated the reduction of food intake by camostat. In addition, Fos-LI in the DVC in response to both exogenous CCK-8 and camostat administration was significantly attenuated by vagotomy, as well as by blocking CCK 1 receptors. These results demonstrate for the first time that reduction of food intake in adult rats by endogenous CCK released by a nonnutrient mechanism requires CCK 1 receptors, the vagus nerve, and activation of the DVC, but not the myenteric plexus. camostat; vagotomy; devazepide Address for reprint requests and other correspondence: Gastroenterology Laboratory, Dept. of Biomedical Sciences, College of Veterinary Medicine, Tuskegee Univ., Tuskegee, AL 36088 (e-mail: sayeghai{at}tuskegee.edu )