Comparison of the equilibrium exchange of nucleosides and 3-O-methylglucose in human erythrocytes and of the effects of cytochalasin B, phloretin and dipyridamole on their transport.
Because of similarities in the physical and molecular properties of the nucleoside and sugar transporters of human erythrocytes and the photoaffinity labeling of the sugar transporter by 8-azidoadenosine (Jarvis et al. (1986) J. Biol. Chem. 261, 11077-11085), we have directly compared the equilibrium exchange of uridine and 3-O-methylglucose in these cells as measured by rapid kinetic techniques under identical experimental conditions. Both the Michaelis-Menten constant and maximum velocity were about 100-fold higher for 3-O-methylglucose exchange than for uridine exchange so that the first order rate constants for both transporters were about the same. When calculated on the basis of the number of nucleoside and sugar carriers per red cell estimated by equilibrium binding of nitrobenzylthioinosine and cytochalasin B, respectively, the turnover numbers for the sugar and nucleoside carriers with 3-O-methylglucose and uridine, respectively, as substrates were quite similar. Various sugars up to concentrations of 108 mM had no effect on the exchange of 500 microM uridine or adenosine, and uridine up to a concentration of 50 mM had no effect on the exchange of 10 mM 3-O-methylglucose. Adenosine, on the other hand, inhibited 3-O-methylglucose exchange in a concentration dependent manner, though not very effectively (IC50 approximately equal to 3 mM). Both uridine and 3-O-methylglucose exchange were inhibited in a concentration dependent manner by cytochalasin B, phloretin and dipyridamole, but cytochalasin B and phloretin were 100-times more effective in inhibiting 3-O-methylglucose than uridine exchange, whereas the opposite was the case for the inhibition by dipyridamole.
D019325:3-O-Methylglucose; D000241:Adenosine / Q000031:analogs & derivatives / Q000097:blood; D000345:Affinity Labels / Q000378:metabolism; D001386:Azides / Q000097:blood; D003571:Cytochalasin B / Q000494:pharmacology*; D004176:Dipyridamole / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008757:Methylglucosides / Q000097:blood*; D008759:Methylglycosides / Q000097:blood*; D009004:Monosaccharide Transport Proteins / Q000097:blood*; D009705:Nucleosides / Q000097:blood*; D010693:Phloretin / Q000494:pharmacology*; D014529:Uridine / Q000097:blood
D000345:Affinity Labels; D001386:Azides; D008757:Methylglucosides; D008759:Methylglycosides; D009004:Monosaccharide Transport Proteins; D009705:Nucleosides; D019325:3-O-Methylglucose; D003571:Cytochalasin B; C012760:8-azidoadenosine; D004176:Dipyridamole; D000241:Adenosine; D010693:Phloretin; D014529:Uridine