Adenosine is produced, released, taken up and metabolized by most animal cells. A strong interest in adenosine developed after the proposition that it may be a major factor in the regulation of myocardial blood flow. There is evidence for the existence of at least two subclasses of adenosine receptor, A1 and A2, on the extracellular side of cell membrane . These receptors have been characterized by biochemical, physiological and pharmacological techniques in many types of tissues. However, in some tissues, namely sympathetic ganglia and renovascular bed, the adenosine receptor subtypes have not been adequately defined. In this study the subtypes of adenosine receptor in sympathetic ganglia and those involved in renal function will be determined by measuring biochemical, pharmacological and electrophysiological changes resulting from activation of these receptors by specific adenosine agonists. The adenosine receptors in sympathetic ganglia of rats will be characterized by determining the order of effectiveness of various agonists (adenosine, 2CLA, L-PIA and DPMA) with different efficacies on A1 and A2 receptor subtypes, on the evoked compound postganglionic action potential as index of ganglionic transmission. The pA2 values of the recently introduced selective adenosine A1 and A2 receptors antagonists will be determined. The linkage of the receptor subtype involved in ganglionic effects of adenosine to cyclic AMP will be studied pharmacologically by pretreating ganglia with agents such as isoproterenol, forskolin and papaverine that increase cyclic AMP levels or those which decrease cyclic AMP level such as SQ 22,536 and imidazole before testing adenosine agonists on evoked action potentials. Biochemical determination of cyclic AMP levels will also be carried out in ganglia. The adenosine receptor subtype in the renovascular, which seems to be species-dependent, will be characterized in perfused kidneys by measuring the effect of agonists on electrically-evoked or norepinephrine-evoked vasoconstriction. The receptor subtype(s) responsible for renin release will also be characterized. Linkage to adenylate cyclase in the renovascular bed will be determined by measuring cyclic AMP level in renal arteries from rats. These experiments should provide important information about the role of adenosine receptors in the control of cardiovascular function.
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