October 24 (Fri.), 9:00–11:00, Room 5 (Portopia Hotel South Wing Ohwada A)
IS-S4-2

Vasoactive intestinal peptide (VIP) is involved in intraperitoneal corticotropin-releasing factor (CRF) induced diarrhea in rats

S. Yakabi1,2
Co-authors: K. Koike2, K. Yakabi3
1
University of California Los Angeles
2
Department of Gastroenterology, The University of Tokyo
3
Department of Gastroenterology and Hepatology, Saitama Medical University
Aim: To investigate whether VIP mediates IP CRF stimulatory effect on defecation and diarrhea in rats. Methods: VIP antagonist or vehicle was co-injected IP with CRF or vehicle. Fecal pellet output (FPO) and diarrhea were monitored for 1 h, then duodenum, jejunum, ileum and proximal colon were collected for whole mount preparations, which were processed for double immunolabeling of Fos and VIP, and VIP and CRF receptor 1 (CRF-R1). Blood and ileum was collected for VIP measurement. Results: CRF increased FPO and induced diarrhea. The VIP antagonist completely prevented CRF effects (8.5±1.0 vs. 2.5±0.8 pellets/h, 1.7±0.3 vs. 0±0 diarrhea score/h n=11-13; p<0.01). CRF increased Fos expression in the submucosal plexus of the ileum and myenteric plexus of the colon. Fos was co-localized in VIP positive neurons in the ileum (92.2%). Fos expression was less in duodenum and few in the jejunum submucosal plexus. VIP antagonist inhibited CRF-induced Fos expression. CRF-R1 was co-localized with VIP in the ileal submucosal neurons. CRF did not influence VIP levels in the plasma but show a trend to increase in the ileum. Conclusions: CRF activates VIP containing submucosal neurons in the ileum possibly through CRF-R1 and plays an important role in CRF-induced diarrhea and increase in FPO.