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The aims of the proposed studies are to evaluate the role of specific neurotransmitters of the enteric nervous system on gastrointestinal regulatory peptide secretion. Gamma-aminobutryic acid and purine nucleotides substances adenosine and adenosine triphosphate (ATP) have been proposed as putative neurotransmitters within the enteric nervous system. Preliminary observations by the principal investigator suggest that GABAergic and purinergic neurotransmitters significantly influence release of the antral regulatory peptides, gastrin and somatostatin. The objectives of the proposed studies are to document the uptake, storage and release of these putative neurotransmitters from antral mucosal/submucosal nerves and to characterize receptor-mediated events which modulate neurotransmitter and gut peptide secretion. The in vitro models employed in these studies (isolated antral mucosal/submucosal fragments and antral submucous plexus isolation) will provide the opportunity to answer a number of fundamental questions about the interrelationships between neurotransmitter release and gut regulatory peptide secretion. It is anticipated that these studies will provide insights into the physiology and pathophysiology of enteric nervous system control over gut endocrine cell secretion.
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