NEURAL REGULATION OF SMALL INTESTINAL MUCOSA

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This is a proposal to continue investigation of intrinsic neural mechanisms that influence intestinal mucosal secretory function in the guinea pig ileum. Studies that utilize Ussing chambers to determine the ionic responses of tissues to putative neurotransmitters will be done in parallel with micorlelectrode studies that will identify direct actions of putative transmitters at the level of identified VIP-ergic neurons. The first specific aim is to clarify the role of VIP-ergic motor neurons in altered ion transport evoked by electrical field stimulation or reflex activation in mucosal preparations in Ussing chambers. The second aim will identify the neurotransmitters that excite VIP-ergic neurons by examining short-circuit current in mucosal preparations in Ussing chambers. The third aim is to establish the neurophysiological mechanisms of action of putative neurotransmitters that alter transport by examining their effects on single VIP-ergic motor neurons. Agonists or antagonists will be added to the superfusion solutions of mucosal sheets containing intact submucosal ganglia to characterize changes in short-circuit current responses. The ionic basis for changes in short-circuit current will be evaluated by determination of radioisotopic measurement of sodium and chloride fluxes. Electrical and synaptic behavior of single VIP-ergic neurons will be determined by placing recording microelectrodes directly into cell bodies of submucosal neurons. Impaled neurons will bc identified unequivocally as VIP-ergic by the presence of Lucifer Yellow fluorescence and avidin-biotin-peroxidase staining in the same cell body. Integration of the Ussing chamber studies with investigations of electrophysiological re- sponses of submucosal ganglion cells to the putative messengers is designed to provide more comprehensive insights into the neurophysiological mechanisms of control of mucosal transport. 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 neural reflex pathways that govern the fluidity of the intestinal contents during normal functioning of the bowel, or during pathophysiological states such as secretory diarrhea.