CRF is a 41 amino acid peptide characterized from the hypothalamus in various animal species and human. CRF like immunoreactivity has been localized in the brain, spinal cord and peripheral tissues including the gastrointestinal tract. Experimental evidence indicates that CRF may be a key signal involved in coordinating organism's response to stress. Based on previous demonstration that CRF acts centrally to stimulate bicarbonate secretion and inhibit gastric acid and emptying of a liquid meal, and that peripheral injection of CRF also suppressed gastric acid secretion and emptying in rats and dogs, the objectives of the application are 1) to map brain sites involved in CRF induced alteration of gastric function glass micropipet injection of CRF into selective nucleus, 2) to elucidate neurohumoral pathways mediating peripheral administration of CRF induced inhibition of gastric acid secretion and emptying by using pharmacological and surgical approaches, evaluating the presence of specific binding sites for CRF in the gut and vagus nerve, and electrophysiological recording of the activity of neurons in the nucleus motor nucleus and other related hind brain nucleus in response to pheripheral CRF injection, 3) to investigate whether endogenous CRF release by stress is involved in stress induced delay in gastric emptying using the selective CRF antagonist, helical CRF 9-41, 4) to establish whether gastric response to intravenous CRF in human is similar to that of experimental animals using automated technique of intragastric titration for monitoring acid secretion, dye-dilution technique for evaluation of gastric emptying of a homogenized solid meal, and multilumen tube for recording gastric motility. All the experiments except project 4 will be performed in rats. Gastric secretion will be collected in conscious pylorus-ligated rats or anesthetized rats with gastric fistula and processed for measurements of variations in acidity, using automated titration, bicarbonate secretion, using a Natelson gasometer and gastric emptying using phenol red method. Such studies will have important implications in the understanding of brain regulation of gastric acid and bicarbonate secretion and gastric emptying, may unravel the underlying mechanisms of stress-induced delay in gastric emptying, and establish the clinical relevance of the previous findings in experimental animals.
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