The major goal of this proposal is to define the action of neuropeptides, administered into the central nervous system (CNS), on net transepithelial fluid and electrolyte transport in the intestine. Although it is recognized that the CNS regulates the activity of the digestive system, the precise mechanisms by which this occurs are not completely understood. A number of peptides, endogenous to the mammalian brain and gut, have been found to alter gastrointestinal functions, such as gastric secretion and intestinal motor activity, after their administration into the brain. However, the CNS actions on ion and fluid transport processes in the gut are unknown. In the present proposal, five families of these substances, eg., opioid peptides, bombesin, somatostatin, thyrotropin-releasing hormone and calcitonin, will be examined by conventional methods for their abilities to modify intestinal fluid and ion transport in the rat intestine after CNS administration. This investigation encompasses four specific objectives: (1) The identification of peptides which, after their administration into the lateral cerebral ventricles, modify net water transport and transmural electrical potential difference (PD) across discrete regions of the small and large intestine in situ. (2) An assessment of the specificity of these CNS effects for intestinal fluid transport through a simultaneous analysis of peptide actions on other physiological parameters (i.e. blood pressure, respiration and intestinal motility). (3) The elucidation of changes in the net transmural fluxes of ions that underlie the effects of peptides on basal and stimulated water transport and PD. (4) An examination of the peripheral neurohumoral mechanisms underlying the CNS actions of peptides on gut fluid transport processes. The results obtained from the proposed experiments will greatly enhance the understanding of the control of digestive system function by the CNS and provide a physiological and neurochemical basis for psychosomatic diseases of the gastrointestinal tract.
