Effect of adenosine on Na+ and Cl- currents in A6 monolayers. Receptor localization and messenger involvement

The effect of adenosine regulation on sodium and chloride transport was examined in cultured A(6) renal epithelial cells. Adenosine and its analogue N-6-cyclopentyladenosine (CPA) had different effects on shea-circuit current (I-sc) depending on the side of addition. Basolateral CPA addition induced an approximately threefold increase of the I-sc that reached a maximum effect 20 min after addition and was completely inhibited by preincubation with either an A(2) selective antagonist, CSC, or the sodium channel blocker, amiloride. Apical CPA addition induced a biphasic I-sc response characterized by a rapid fourfold transient increase over its baseline followed by a decline and a plateau phase that were amiloride insensitive. The A(1) adenosine antagonist, CPX, completely prevented this response. This I-sc response to apical CPA was also strongly reduced in Cl--free media and was significantly inhibited either by basolateral bumetanide or apical DPC preincubation. Only basolateral CPA addition was able to induce an increase in cAMP level. CPA, added to cells in suspension, caused a rapid rise in [Ca2+](i) that was antagonized by CPX, not affected by CSC and prevented by thapsigargin preincubation. These data suggest that basolateral CPA regulates active sodium transport via A(2) adenosine receptors stimulating adenylate cyclase while apical CPA regulates Cl- secretion via A(1) receptor-mediated changes in [Ca2+](i)