The main objectives will be to provide a better insight on the role of brain neuropeptides in central regulation of gastric secretory and motor functions. Selecting neuropeptides previously demonstrated to act within the brain to stimulate or to inhibit gastric acid secretion, we will 1) further localize and map specific sites in rat brain responsive to peptides by studying changes in gastric secretion and motility evoked by microinfusions of these peptides in specific cortical, hypothalamic, brain stem and spinal structures. 2) study neural pathways involved in mediating peptides action using electrophysiologic approaches of extracellular recording of neuron activity from sensitive sites localized in section 1 and gastric branch of the autonomic nervous system. 3) further characterize CNS and peripheral neurotransmitters or hormones mediating peptide action using pharmacologic or surgical approaches. 4) evaluate the possible physiologic role of these peptides in the central control of gastric secretion using selective antagonists when available and passive immunization. Peptides mostly studied will be bombesin, TRH, somatostatin, oxytocin, arginine vasopressine. Gastric secretions will be collected in conscious pylorus-ligated rats or gastric fistula dogs or in anesthetized rats with gastric fistula and processed for measurement of variations in volume, titratable acidity, pepsin and gastrin. Gastric contractions will be monitored by implanting extraluminal strain gages onto the corpus. Recording of the efferent autonomic nerve activity will be performed using platinum electrodes positioned on gastric branch of the vagus and splanchnic nerve, of single cell unit using the technique of combined iontophoresis and single cell microelectrode recording. Such studies will yield substantive information on brain structures and neural pathways involved in the CNS regulation of gastric function, lead to significant progress in the knowledge of central peptidergic modulation of the autonomic nervous system outflow to the gastrointestinal tract and ultimately the physiologic relevance of specific brain neuropeptides in mediating brain-gut-brain interactions in health and disease.
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