1999
DOI: 10.1007/s002329900496
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New Drugs for the Na + /H + Exchanger. Influence of Na + Concentration and Determination of Inhibition Constants with a Microphysiometer

Abstract: Abstract. The NHE-1 isoform of the Na + /H + exchanger is excessively activated in cardiac cells during ischemia. Hence NHE-1 specific inhibitors are being developed since they could be of beneficial influence under conditions of cardiac ischemia and reperfusion. In this study, the Cytosensor microphysiometer was used to measure the potency of four new drug molecules, i.e., EMD 84021, EMD 94309, EMD 96785 and HOE 642 which are inhibitors of the isoform 1 of the Na + /H + exchanger. The experiments were perform… Show more

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Cited by 34 publications
(19 citation statements)
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“…All inhibitors were purchased from Sigma with the exception of EMD 96785 (17,18), which was a generous gift from Dr. Norbert Beier, Merck KGaA. Stock solutions of amiloride, EIPA, EMD 96785, and bafilomycin A 1 were prepared in dimethyl sulfoxide (Me 2 SO); DCCD was dissolved in ethanol; N-ethylmaleimide (NEM) and vanadate were dissolved in water.…”
Section: Methodsmentioning
confidence: 99%
See 1 more Smart Citation
“…All inhibitors were purchased from Sigma with the exception of EMD 96785 (17,18), which was a generous gift from Dr. Norbert Beier, Merck KGaA. Stock solutions of amiloride, EIPA, EMD 96785, and bafilomycin A 1 were prepared in dimethyl sulfoxide (Me 2 SO); DCCD was dissolved in ethanol; N-ethylmaleimide (NEM) and vanadate were dissolved in water.…”
Section: Methodsmentioning
confidence: 99%
“…3, B and C, respectively). However, EMD 96785, a more potent and more selective inhibitor of at least some of the mammalian NHE isoforms (17,18), caused only a slight (although significant) decrease in pH i when added at a concentration (500 M) more than 3 orders of magnitude higher than its IC 50 values for the inhibition of mammalian NHE1 and NHE2 (Refs. 17 and 18; Fig.…”
Section: Effect Of Extracellular Namentioning
confidence: 99%
“…The microphysiometer was developed as a pH sensor to detect the changes of cell activity in response to a variety of stimuli (McConnell et al, 1992;Owicki et al, 1990;Fischer et al, 1999). In the original manual of this apparatus, pH changes in the extracellular medium were measured as total acidification during ''flow off'' of a relatively long period (60 -180 s) (McConnell et al, 1992).…”
Section: Discussionmentioning
confidence: 99%
“…Its molecular function is the electroneutral, reversible exchange of Na + against H + . The activation of Na + /H + antiporter results in intracellular alkalization due to the transport of H + out of the cell [16]. Therefore, it is possible that following the pattern described for noradrenaline [15], the increase in [Ca 2+ ] i activates Na + /H + antiporter.…”
Section: Discussionmentioning
confidence: 99%