Ouabain-insensitive acidification by dopamine in renal OK cells:: primary control of the Na+/H+ exchanger

The present study was aimed at evaluating the role of D-1- and D-2-like receptors and investigating whether inhibition of Na+ transepithelial flux by dopamine is primarily dependent on inhibition of the apical Na+/H+ exchanger, inhibition of the basolateral Na+-K(+)ATPase, or both. The data presented here show that opossum kidney cells are endowed with D-1- and D-2-like receptors, the activation of the former, but not the latter, accompanied by stimulation of adenylyl cyclase (EC50 =220 +/- 2 nM), marked intracellular acidification (IC50 = 58 +/- 2 nM), and attenuation of amphotericin B-induced decreases in short-circuit current (28.6 +/- 4.5% reduction) without affecting intracellular pH recovery after CO2 removal. These results agree with the view that dopamine, through the activation of D-1- but not D-2-like receptors, inhibits both the Na+/H+ exchanger (0.001933 +/- 0.000121 vs. 0.000887 +/- 0.000073 pH unit/s) and Na+-K+-ATPase without interfering with the Na+ independent HCO3- transporter. It is concluded that dopamine, through the action of D-1- like receptors, inhibits both the Na+/H+ exchanger and Na+-K+-ATPase, but its marked acidifying effects result from inhibition of the Na+/H+ exchanger only, without interfering with the Na+-independent HCO3- transporter and Na+-K+-ATPase.