PT  - JOURNAL ARTICLE
AU  - Casavola, V.
AU  - Guerra, L.
AU  - Reshkin, S. J.
AU  - Jacobson, K. A.
AU  - Murer, H.
TI  - Polarization of Adenosine Effects on Intracellular pH in A<sub>6</sub> Renal Epithelial Cells
DP  - 1997 Mar 01
TA  - Molecular Pharmacology
PG  - 516--523
VI  - 51
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/51/3/516.short
4100  - http://molpharm.aspetjournals.org/content/51/3/516.full
SO  - Mol Pharmacol1997 Mar 01; 51
AB  - The effect of adenosine on Na+/H+ exchange activity was examined in cultured A6 renal epithelial cells. Adenosine and its analogue N6-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 A2A-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 A1-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 pHi during hormone action can act as an intermediate in the second-messenger cascade. The American Society for Pharmacology and Experimental Therapeutics