S3226, a novel inhibitor of Na+/H+ exchanger subtype 3 in various cell types |
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Authors: | Jan-Robert Schwark Hans Willi Jansen Hans-Jochen Lang Wolfgang Krick Gerhard Burckhardt M. Hropot |
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Affiliation: | Hoechst AG, Hoechst Marion Roussel, H 821, D-65926 Frankfurt am Main, Germany, DE Zentrum Physiologie und Pathophysiologie, Universit?t G?ttingen, Humboldtallee 23, D-37073 G?ttingen, Germany, DE
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Abstract: | Inhibition of Na+/H+ exchange (NHE) subtypes has been investigated in a study of the mouse fibroblast L cell line (LAP1) transfected with human (h) NHE1, rabbit (rb) NHE2, rat (rt) or human (h) NHE3 as well as an opossum kidney cell line (OK) and porcine renal brush-border membrane vesicles (BBMV). S3226 {3-[2-(3-guanidino-2-methyl-3-oxo-propenyl)-5-methyl-phenyl]-N-isopropylidene-2-methyl-acrylamide dihydro-chloride} was the most potent and specific NHE3 inhibitor with an IC50 value of 0.02 μmol/l for the human isoform, whereas its IC50 value for hNHE1 and rbNHE2 was 3.6 and @80 μmol/l, respectively. In contrast, amiloride is a weak NHE3 inhibitor (IC50>100 μmol/l) with a higher affinity to hNHE1 and rbNHE2. Cariporide (4-isopropyl-3-methylsulphonyl-benzoyl-guanidine methane-sulphonate), which has an IC50 for NHE3 of approximately 1 mmol/l, is a highly selective NHE1 inhibitor (0.08 μmol/l). Therefore, S3226 is a novel tool with which to investigate the physiological and pathophysiological roles of NHE3 in animal models. Received: 14 May 1998 / Received after revision: 29 June 1998 / Accepted: 2 July 1998 |
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Keywords: | BCECF Brush border membrane vesicles (BBMV) Fibroblasts Na+/H+ exchange NHE3 inhibitor Opossum kidney |
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