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 myocardial blood flow. There is evidence for the existence of two subclasses, A(1) and A(2) of cell membrane adenosine receptors on the extracellular side. 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 proposed 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 effects of the agonists, adenosine, 2CLA, L-PIA and NECA on the evoked compound postganglionic action potential as index of ganglionic transmission. The linkage of the receptor subtype involved in ganglionic effects of adenosine to cyclic AMP will be studied pharmacologically pretreating ganglia with agents such as isoproterenol, NaF and papaverine that increase cyclic AMP levels or those which decrease cyclic ANP level such as 2',5'-dideoxyadenosine before testing adenosine agonists on evoked action potentials. Biochemical determination of cyclic AMP levels will also be carried out in ganglia from SHR and WKY rats. The adenosine receptor subtype in the renovascular, which seems to be species-dependent, will be characterized in SHR and WKY and in rabbit perfused kidney by measuring the effect of agonist on electrically-evoked or norepinephrine-evoked vasoconstriction. The receptor subtype responsible for renin release will also be characterized. Coupling to adenylate cyclase in the renovascular bed will be determined by measuring cyclic AND level in renal arteries from rabbits, SHR and WKY rats. These experiments should provide important information about the role of adenosine receptors in control of blood pressure in normal and hypertensive states.
NIH ExPorter
NIH ExPorter