Acetazolamide inhibition of basolateral base exit in rabbit renal proximal tubule S2 segment.
The influence of the carbonic anhydrase inhibitor acetazolamide (ACZ) was investigated on HCO3- transport mechanisms in the basolateral cell membrane of rabbit renal proximal tubule. Experiments were performed on isolated S2 segments using double-barrelled microelectrodes to measure cell membrane potential (Vb) and cell pH (pH(i)) during step changes in bath perfusate ion concentrations. Peritubular application of ACZ (1 mmol/l) reduced the initial Vb response to 10:1 reduction of bath HCO3- concentration only slightly, from +53.8 +/- 4.2 mV to +49.1 +/- 0.3 mV (n = 5), but caused an intermittent overshooting repolarization in the secondary Vb response. In conjunction with these effects it left the initial pH(i)) response virtually unchanged but induced a secondary slow acidification. These observation indicate that--under the present experimental conditions--ACZ does not block the Na(+)-HCO3- cotransporter but acts via inhibition of cytosolic carbonic anhydrase. This was confirmed by studying the effect of elevated intracellular HCO3- concentrations under reduced flux conditions and by comparing the concentration dependence of the Vb response with the inhibition kinetics of cytosolic carbonic anhydrase. In contrast, peritubular ACZ inhibited Na(+)-independent Cl-/HCO3- exchange in the basolateral cell membrane of S2 segments directly in a similar way to that described in the preceding publication for S3 segments.
Seki
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Zentrum der Physiologie, J.W. Goethe Universität, Frankfurt/Main, Federal Republic of Germany.
Frömter
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D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002245:Carbon Dioxide / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D004594:Electrophysiology; D005260:Female; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D009994:Osmolar Concentration; D010313:Partial Pressure; D011817:Rabbits; D027982:Sodium-Bicarbonate Symporters
D001639:Bicarbonates; D002352:Carrier Proteins; D027982:Sodium-Bicarbonate Symporters; D002245:Carbon Dioxide; D000086:Acetazolamide