Previously, we obtained evidence that specific neuropeptides, such as bombesin-like peptides, thyrotropin-releasing factor, corticotropin-releasing factor, somatostatin, opioid peptides and calcitonin gene-related peptide, act within the brain to influence gastric secretion, contractility and emptying and the ulcerogenic response to stress. These findings and reports by other investigators have delineated a new concept related to brain peptidergic regulation of gastric function. The objectives of the research program will be to develop further such field of investigation to reach a better understanding of brain regulation of gastric secretory and motor function.
The specific aims will be 1) to localize brain sites of action of bombesin, TRH, and CRF to influence gastric function and stress ulceration using microinjection of peptides in specific brain nucleus containing nerve terminal fibers and/or receptors for these peptides 2) to elucidate the neurohumoral pathways mediating the information from brain sites to the stomach using surgical, pharmacological and electrophysiological techniques, 3) to assess the physiologic role of these peptides using selective antagonists and passive immunization. Such studies will yield important information on brain structures, pathways and neurotransmitters involved in brain regulation of gastric function and have relevant implications in the understanding of the pathogenesis of stress ulcer and eating disorders associated with alteration of gastric emptying.
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