Basolateral and apical A1 adenosine receptors mediate sodium transport in cultured renal epithelial (A6) cells

There are conflicting reports in the literature regarding the adenosine receptor that mediates the increase in sodium transport in the A6 cell. In this study we used specific A(1) and A(2) adenosine receptor agonists and antagonists, as well as two different subclones of the A6 cell, to determine which adenosine receptor mediates the increase in sodium transport. In the A6S2 subclone, basolateral and apical N(6)-cyclohexyladenosine (CHA), a selective A(1) receptor agonist, stimulated sodium transport at a threshold concentration <10(-7) M, whereas CGS-21680, a selective A(2) receptor agonist, had a threshold concentration that was at least 10(-5) M. The A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) was found to have a nonspecific effect on CHA-stimulated sodium transport, whereas the A(2) receptor antagonist 8-(3-chlorostyryl) caffeine (CSC) had no effect. As with the A6S2 subclone, basolateral and apical CHA stimulated sodium transport at a nanomolar concentration in the A6C1 subclone and the threshold concentration for CGS-21680 was in the high micromolar range. Concurrent with the increase in sodium transport, CHA also stimulated anion secretion in the A6C1 subclone. These data demonstrate that adenosine increases sodium transport via the A(1) receptor in different subclones of the A6 cell, including a subclone capable of anion secretion.