Kinetic mechanism of chlorpromazine inhibition of erythrocyte 3-O-methylglucose transport.
The kinetic mechanism of chlorpromazine inhibition of erythrocyte hexose transport was investigated using the non-metabolizable glucose analog 3-O-methylglucose. It was found that chlorpromazine added to the external medium is a non-competitive inhibitor of both equilibrium exchange and net 3-O-methylglucose transport at pH 7.8, 15 degrees C. The Ki for equilibrium exchange is 76 +/- 21 microM. When net efflux and equilibrium exchange were measured on the same population of cells the equilibrium exchange was 2.5-times the maximum net efflux. The percent reduction of 3-O-methylglucose flux by chlorpromazine is dependent upon chlorpromazine concentration and not 3-O-methylglucose concentration as expected for a non-competitive inhibitor. Equilibrium exchange and net efflux show the same extent of inhibition at each concentration of chlorpromazine evaluated. These results suggest that exchange and net efflux of 3-O-methylglucose in the human erythrocyte may share a common transport system.
D019325:3-O-Methylglucose; D001693:Biological Transport, Active / Q000187:drug effects; D002746:Chlorpromazine / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008757:Methylglucosides / Q000097:blood*; D008759:Methylglycosides / Q000097:blood*
D008757:Methylglucosides; D008759:Methylglycosides; D019325:3-O-Methylglucose; D002746:Chlorpromazine