NEURAL REGULATION OF INTESTINAL MUCOSA

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This study is designed to examine intrinsic neural mechanisms that influence intestinal mucosal secretory function in the guinea pig ileum. The first objective is to identify neurotransmitters that influence mucosal function within the synaptic circuitry of the submucosal plexus, and at neuroepithelial junctions. The second aim is to identify neurotransmitters that are involved in a reflex pathway that influences intestinal ion transport processes when glucose is removed from the mucosal buffer solutions. The studies will be done on flat sheet preparations of guinea pig ileum that have had the muscularis externa removed by blunt dissection. The guinea pig ileum is the best animal model for studying neural regulation of mucosal function because the types of enteric nerves within the submucosal plexus have been identified, and the electrophysiological properties of the enteric neurons have been reported. The tissues will be mounted in Ussing flux chambers that are modified for electrical field stimulation of intramural neurons, and changes in short-circuit current and ion fluxes will be measured during electrical activation of enteric nerves. The principal methods for identifying the types of nerves that influence the mucosa will be pharmacological analyses and assays for putative neurotransmitters that are released into the bath during electrical field stimulation. The proposed study will expand the very limited knowledge of ion transport processes in the guinea pig and of the neurophysiological mechanisms that control small intestinal transport function. It will provide new information on reflex pathways that may govern the fluidity of the intestinal contents during normal functioning of the bowel, or during pathophysiological states such as secretory diarrhea.