title: Bumetanide inhibits (Na + K + 2Cl) co-transport at a chloride site.
abstract: Chloride-dependent cation transport systems in a number of cells and tissues are inhibited by 5-sulfamoylbenzoic acid loop diuretics, such as furosemide and bumetanide. Interactions between chloride and bumetanide have been examined in the catecholamine-activated (Na + K + 2Cl) co-transport pathway of the duck red blood cell. Levels of chloride were varied while maintaining a constant ratio of internal to external chloride across the cell membrane. Increasing external chloride from 20 to 100 mM shifted the dose-response curve for the effect of bumetanide on co-transport toward higher concentrations of the drug. The bumetanide concentration producing half-maximal inhibition (IC50) was increased from approximately 6 X 10(-8) to approximately 2 X 10(-7) M. When cells were incubated in the presence of a constant, submaximal inhibitory dose of bumetanide (10(-8) M), increasing external chloride (in increments of 20 mM) from 20 to 140 mM progressively decreased the level of inhibition of the co-transport system. Kinetic analysis of the data demonstrates that bumetanide and chloride compete for a common site.
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002034:Bumetanide / Q000494:pharmacology*; D002712:Chlorides / Q000097:blood*; D004232:Diuretics / Q000494:pharmacology*; D004372:Ducks; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008094:Lithium / Q000097:blood; D011188:Potassium / Q000097:blood*; D012413:Rubidium / Q000097:blood; D012964:Sodium / Q000097:blood*
chemical_list: D002712:Chlorides; D004232:Diuretics; D002034:Bumetanide; D008094:Lithium; D012964:Sodium; D012413:Rubidium; D011188:Potassium