The interaction of amiloride analogues with the Na+/H+exchanger in kidney medulla microsomes

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Abstract

The effects of ten amiloride analogues on Na+-H+exchange in rabbit kidney medulla microsomes have been examined. Most of the analogues appeared to inhibit Na+uptake into the microsomes more effectively than did amiloride either in the presence or absence of a pH gradient. However, the analogues were also capable of stimulating Na+efflux from the microsomes at concentrations somewhat higher than the concentrations at which they inhibited Na+influx. The concentrations at which the analogues stimulated Na+efflux were about 2-4-times higher than the concentrations at which they blocked influx. This suggested that the two processes were related. The analogues that stimulated efflux most effectively (the 5-N-benzylamino analogue of amiloride and the 5-N-butyl-N-methylamino analogue) were shown to induce completely reversible effects. These analogues did not stimulate l-[3H]glucose efflux from medulla microsomes which ruled out nonspecific vesicle destruction or reversible detergent effects. These analogues also induced Na+efflux from microsomes in the presence of high concentrations of added buffer, which ruled out weak-base uncoupling effects. The possibility exists that these analogues are carried into the microsomes via the Na+-H+exchange protein and that this permits them to both block Na+influx into the microsomes and stimulate Na+efflux as well. © 1984.

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Labelle, E. F., Woodard, P. L., & Cragoe, E. J. (1984). The interaction of amiloride analogues with the Na+/H+exchanger in kidney medulla microsomes. BBA - Biomembranes, 778(1), 129–138. https://doi.org/10.1016/0005-2736(84)90456-5

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