S3226, a novel inhibitor of Na+/H+ exchanger subtype 3 in various cell types

• Published in: Pflügers Archiv Vol. 436; no. 5; pp. 797 - 800
• Main Authors: Schwark, J R, Jansen, H W, Lang, H J, Krick, W, Burckhardt, G, Hropot, M
• Format: Journal Article
• Language: English
• Published: Germany Springer Nature B.V 01.10.1998
• Subjects: Amiloride - pharmacology; Animals; Cell Line; Dose-Response Relationship, Drug; Guanidines - metabolism; Guanidines - pharmacology; Humans; Ion Channels - antagonists & inhibitors; Methacrylates - metabolism; Methacrylates - pharmacology; Mice; Microvilli - drug effects; Opossums; Proteins; Rabbits; Rats; Rodents; Small intestine; Sodium-Hydrogen Exchanger 3; Sodium-Hydrogen Exchangers - antagonists & inhibitors; Stereoisomerism; Studies; Sulfones - pharmacology; Swine
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s004240050704

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-isopro pylidene-2-methyl-acrylamide dihydro-chloride¿ was the most potent and specific NHE3 inhibitor with an IC50 value of 0.02 micromol/l for the human isoform, whereas its IC50 value for hNHE1 and rbNHE2 was 3.6 and approximately = 80 micromol/l, respectively. In contrast, amiloride is a weak NHE3 inhibitor (IC50>100 micromol/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 micromol/l). Therefore, S3226 is a novel tool with which to investigate the physiological and pathophysiological roles of NHE3 in animal models.