Duodenal myotomy blocks reduction of meal size and prolongation of intermeal interval by cholecystokinin

We have shown that vagotomy (VGX) attenuates the reduction of meal size (MS) produced by cholecystokinin (CCK) -8 and -33 and that celiaco-mesenteric ganglionectomy (CMGX) attenuates the prolongation of the intermeal interval (IMI) produced by CCK-33. Here, we report the following novel data. First, by determining the distribution of CCK1 receptor messenger RNA, which mediates reduction of MS and prolongation of IMI by CCK, in seven regions of the gastrointestinal tract in the adult rat we found that the duodenum contains the highest concentration of this receptor in the gut. Second, based on the previous finding we performed a unique surgical technique known as duodenal myotomy (MYO), which severs all the nerves of the gut wall in the duodenum including vagus, splanchnic and enteric nerves. Third, we determined MS and IMI in duodenal MYO rats in responses to endogenous CCK-58 released by the non-nutrient, trypsin inhibitor, camostat and CCK-8 to test the possibility that the duodenum is the site of action for reduction of MS and prolongation of IMI. We found that, similar to the previous work reported by using CCK-8 and MS, duodenal MYO also blocked reduction of MS by camostat. Forth, duodenal MYO blocked prolongation of IMI by camostat. As such, our current results suggest that the duodenum is the gut site that communicates both feeding signals of endogenous CCK, MS and IMI, with the brain through vagal and splanchnic afferents.

► The distribution of CCK1 receptor in the gut of the rat is not reported. ► The exact gut site of action that prolong IMI by endogenous CCK is not known. ► Duodenal myotomy (MYO) is a unique surgery that severs vagus, splanchnic and enteric nerves. ► Duodenal MYO blocked reduction of MS and prolongation of IMI by camostat. ► The duodenum is a gut site that communicates MS and IMI by camostat with the brain.