Corticotropin-releasing factor (CRF) is a 41-amino acid peptide recently characterized from ovine hypothalamus which exerts a physiologic role in the regulation of ACTH secretion. CRF has also been shown to act within the brain to trigger various behavioral, endocrine and cardiovascular response characteristic of stress. Our preliminary data indicate that intracisternal or intravenous ovine CRF markedly inhibits gastric acid secretion. The main objective of the research project is to bring more insight into the biological role of CRF in the regulation of gastric function under normal and stress conditions. To accomplish such aims, the research plan will focus on 4 major questions 1) to characterize the effects of intracerebral and peripheral administration of CRF on gastric secretory function by measuring changes in acid, pepsin, mucus, and gastrin secretion in rats and in dogs; 2) to localize the brain structures involved in the central nervous system action of CRF to influence gastric secretion using pressure or iontophoretic application of the peptide in selective sites; 3) to elucidate the neurohumoral pathways and mechanisms mediating gastric response to CRF using surgical and pharmacological approachs to block the autonomic nervous system, pituitary or adrenal hormone secretion and studying the interaction of CRF with other neuropeptides known to influence gastric secretion (somatostatin, dynorphin) and the cellular localization of CRF-LI in gastrointestinal tract; 4) to evaluate the role of endogenous CRF in gastric response to stress using passive immunization, direct measurement of CRF-LI in selective brain area, and body fluid (portal blood, and gastric intestinal fluid). Knowledge generated by these studies will bring an original contribution to the peptidergic brain-gut axis field and will have important implications for understanding the molecular mechanisms underlying gastric physiopathologic response to stress.
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