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• W1965243900 abstract "Part of the natriuretic mechanism of dihydropyridine Ca 2+ channel antagonists involves the inhibition of renal tubular sodium reabsorption. To identify the membrane ion transport system involved in this natriuretic action, we tested nitrendipine on unidirectional 86 Rb + fluxes in Madin-Darby canine kidney (MDCK) cells. To dissect between direct and indirect effects (via cytosolic Ca 2+ ) of nitrendipine, the compound was re-examined on ion fluxes in human erythrocytes. In MDCK cells, external Ca 2+ (3 mM), adrenalin (100 μM) and the Ca 2+ ionophore A23187 (20 μM) strongly and transiently stimulated 86 Rb + efflux. All these stimulatory actions were fully inhibited by quinine (1 mM) suggesting that they reflect the opening of Ca 2+ -sensitive K + channels. Nitrendipine was able to inhibit these Ca 2+ -sensitive K + channels, but this inhibitory action required high concentrations of the compound (≈ 100 μM). Regarding 86 Rb + influx, the most significant result with nitrendipine was a partial inhibition of bumetanide-sensitive 86 Rb + influx. This effect represented a maximal flux inhibition of about 70% and required very low nitrendipine concentrations (IC 50 ≈ 1 nM). The Ca 2+ ionophore A 23187 strongly stimulated bumetanide-sensitive 86 Rb + influx in MDCK cells. Conversely, a very important reduction (≈ 79%) of this influx component was found in Ca 2+ depleted cells. In human red blood cells, Na + , K + , Cl − contransport fluxes were ressistant to nitrendipine, even at high concentrations of the compound (100–500 μM). Conversely, Ca 2+ -sensitive K + channels were inhibited by nitrendipine with IC 50 = 6±3 μM (mean ± S.E.M., n = 3). In conclusion, nitrendipine is an inhibitor of Ca 2+ -sensitive K + channels and a partial inhibitor of the Na + , K + , Cl − contransport system in MDCK cells. The cotransport inhibitory action, but not that on K + channels, was observed at pharmacological concentrations of nitrendipine. This cotransport inhibition is probably mediated via a decrease in cytosolic free Ca 2+ contents. The physiological relevance of these findings and the link with the natriuretic effect of nitrendipine deserves further investigation." @default.
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• W1965243900 date "1995-04-01" @default.
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• W1965243900 title "Inhibition by nitrendipine of 86Rb+ fluxes in subconfluent MDCK cells" @default.
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• W1965243900 doi "https://doi.org/10.1016/0922-4106(95)90102-7" @default.
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