Abstract
The influence of the carbonic anhydrase inhibitor acetazolamide (ACZ) was investigated on HCO −3 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 (V b) and cell pH (pHi) during step changes in bath perfusate ion concentrations. Peritubular application of ACZ (1 mmol/l) reduced the initial V b response to 10∶1 reduction of bath HCO −3 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 V b response. In conjunction with these effects it left the initial pHi response virtually unchanged but induced a secondary slow acidification. These observation indicate that — under the present experimental conditions — ACZ does not block the Na+-HCO −3 cotransporter but acts via inhibition of cytosolic carbonic anhydrase. This was confirmed by studying the effect of elevated intracellular HCO −3 concentrations under reduced flux conditions and by comparing the concentration dependence of the V b response with the inhibition kinetics of cytosolic carbonic anhydrase. In contrast, peritubular ACZ inhibited Na+-independent Cl−/HCO −3 exchange in the basolateral cell membrane of S2 segments directly in a similar way to that described in the preceding publication for S3 segments.
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Seki, G., Frömter, E. Acetazolamide inhibition of basolateral base exit in rabbit renal proximal tubule S2 segment. Pflugers Arch. 422, 60–65 (1992). https://doi.org/10.1007/BF00381514
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DOI: https://doi.org/10.1007/BF00381514