ADENOSINE RECEPTORS AND ION TRANSPORT IN EPITHELIA

这项应用的目的是确定腺苷和 腺苷受体在调节肾和肾组织离子转运中的作用 肠上皮细胞。具体地说，我们建议研究 腺苷类似物和腺苷受体拮抗剂对跨上皮细胞的作用 鲨鱼直肠腺、哺乳动物直肠腺三种上皮细胞的离子转运 回肠和哺乳动物的肾小管。然后我们将相互关联 腺苷受体对腺苷环化酶离子转运的影响 膜制剂中的活性和特定结合的表征 这些组织中腺苷受体的激动剂和拮抗剂。 采用的方法包括鲨鱼直肠腺的体外灌流， 兔回肠和肾脏的电学测量和离子通量研究 培养中的肾小管细胞，腺苷环化酶活性的测定和 腺苷激动剂和拮抗剂放射性配基的特异性结合 这些上皮细胞的离体膜，~3H腺苷摄取的研究和 膜囊制剂中的转运及腺苷的测定 细胞外介质和组织。该提案将检验这一假设 腺苷的外细胞膜受体存在于 肠细胞和肾小管细胞，是离子的生理调节 在这些上皮细胞中运输。

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.