Renal adenosine A3 receptors in the rat: assessment of functional role

The functional roles of adenosine A3 receptors in the rat kidney were assessed for the first time with respect to A1 receptor-mediated responses. Utilizing a chronically instrumented conscious rat preparation, we tested renal excretory responses to acute administration of the A3 receptor antagonists 3-ethyl-5-benzyl-2-methyl-6-phenyl-4-phenylethynyl-1 ,4-(+)-dihydropridine-3,5-dicarboxylate (MRS-1191) and 9-chloro-2-(2-furyl)-5-phenylacetylamino-[1,2,4]-triazolo[1,5-c]qu inazoline (MRS-1220) with reference to the effects of the A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). The intravenous administration of DPCPX resulted in significant increases in fluid and sodium excretions without affecting glomerular filtration rate (GFR). This suggests that DPCPX-induced diuretic and natriuretic responses are related to decreased tubular reabsorption. However, neither MRS-1191 nor MRS-1220 alone affected fluid or sodium excretions, or GFR, indicating lack of an effect of either compound on renal function. On the other hand, the co-administration of MRS-1220 with DPCPX abolished both the diuretic and natriuretic responses to DPCPX, being suggestive of antagonism between these two compounds. MRS-1191, however, did not affect the DPCPX-induced fluid and sodium excretions. Neither the A1 nor the A3 receptor antagonists altered potassium excretion individually or in combination. The data suggest that while adenosine A1 receptors are involved in the regulation of renal fluid and sodium transport, A3 receptors do not appear to have a major role in regulation of renal excretory function under baseline physiological conditions.