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]quinazoline (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.