Renal adenosine A(3) receptors in the rat: assessment of functional role

The functional roles of adenosine A(3) receptors in the rat kidney were ass essed for the first time with respect to A(1) receptor-mediated responses. Utilizing a chronically instrumented conscious rat preparation, we tested r enal excretory responses to acute administration of the A(3) receptor antag onists 3-ethyl-5-benzyl-2-methyl-6-phenyl-4-phenylethynyl-1,4-(+)-dihydropr idine-3,5-dicarboxylate (MRS-1191) and 9-chloro-2-(2-furyl)-5-phenylacetyla mino-[1,2,4]-triazolo[1,5-c]quinazoline (MRS-1220) with reference to the ef fects of the A(1) receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (D PCPX). The intravenous administration of DPCPX resulted in significant incr eases in fluid and sodium excretions without affecting glomerular filtratio n rate (GFR). This suggests that DPCPX-induced diuretic and natriuretic res ponses are related to decreased tubular reabsorption. However, neither MRS- 1191 nor MRS-1220 alone affected fluid or sodium excretions, or GFR, indica ting lack of an effect of either compound on renal function. On the other h and, the co-administration of MRS-1220 with DPCPX abolished both the diuret ic and natriuretic responses to DPCPX, being suggestive of antagonism betwe en these two compounds. MRS-1191, however, did not affect the DPCPX-induced fluid and sodium excretions. Neither the A(1) nor the A(3) receptor antago nists altered potassium excretion individually or in combination. The data suggest that while adenosine A(1) receptors are involved in the regulation of renal fluid and sodium transport, A(3) receptors do not appear to have a major role in regulation of renal excretory function under baseline physio logical conditions.