POLARIZATION OF ADENOSINE EFFECTS ON INTRACELLULAR PH IN A6 RENAL EPITHELIAL CELLS

The effect of adenosine on Na + /H + exchange activity was examined in cultured A 6 renal epithelial cells. Adenosine and its analogue N 6 -cyclopentyladenosine (CPA) had different effects on Na + /H + exchange activity depending on the side of addition. Basolateral CPA induced a stimulation of Na + /H + exchange activity that was completely prevented by preincubation with an A 2A -selective antagonist, 8-(3-chlorostyryl)caffeine, whereas apical CPA induced a slight but significant inhibition of Na + /H + exchange activity that was significantly reduced by the A 1 -receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine. Protein kinase C activation may be involved in mediating the apical CPA inhibition of Na + /H + exchange activity; this inhibition was prevented by the protein kinase C inhibitor calphostin C. Treatment with either forskolin or 8-bromo-cAMP significantly stimulated Na + /H + exchange activity; only basolateral CPA addition induced an increase in cAMP level. These observations together with the finding that the CPA-dependent stimulation of exchange activity was prevented by the protein kinase A inhibitor H-89 support the hypothesis that basolateral CPA stimulates Na + /H + exchange via adenylate cyclase/protein kinase A activation. Basolateral CPA also increased transepithelial Na + transport, and this stimulation was prevented by the Na + /H + exchange inhibitor HOE-694, suggesting that changes in pH i during hormone action can act as an intermediate in the second-messenger cascade.