The aim of this application is to identify the role of adenosine and adenosine receptors in the regulation of ion transport in renal and intestinal epithelia. Specifically, we propose to examine the effect of adenosine analogs and adenosine-receptor antagonists on trans-epithelial ion transport in three epithelia, the shark rectal gland, the mammalian ileum and mammalian renal tubules. We will then correlate adenosine-receptor mediated effects on ion transport with adenylate cyclase activities in membrane preparations and characterize the specific bindings of agonists and antagonists to adenosine receptors in these tissues. Method to be employed include in vitro perfusion of shark rectal glands, electrical measurements and ion flux studies in the rabbit ileum and kidney tubular cells in culture, measurement of adenylate cyclase activity and specific binding of radioligands of adenosine agonists and antagonists in isolated membranes of these epithelia, studies of 3H adenosine uptake and transport in membrane vesicle preparations and measurements of adenosine in extracellular media and tissue. The proposal will examine the hypothesis that external cell membrane receptors for adenosine, are present on enterocytes and renal tubular cells and are physiologic regulators of ion transport in these epithelia.
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