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 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.
Casavola
V
V
Institute of General Physiology, University of Bari, Italy. casavola@bioserver.uniba.it
Guerra
L
L
Reshkin
S J
SJ
Jacobson
K A
KA
Murer
H
H
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D006859:Hydrogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007668:Kidney; D058915:Purinergic P1 Receptor Antagonists; D012964:Sodium / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014982:Xenopus laevis
D058915:Purinergic P1 Receptor Antagonists; C048599:N(6)-cyclopentyladenosine; D006859:Hydrogen; D012964:Sodium; D000242:Cyclic AMP; D000241:Adenosine; D013755:Tetradecanoylphorbol Acetate