Inhibition of ascorbic acid transport in human neutrophils by glucose.
Because of the structural similarity between glucose and ascorbic acid, we investigated the effect of glucose on uptake and accumulation of ascorbic acid in isolated normal human neutrophils. Ascorbic acid accumulation was determined using high-performance liquid chromatography with coulometric electrochemical detection, in conjunction with liquid scintillation spectrometry. Ascorbic acid accumulation in neutrophils is mediated by a high and a low affinity transport activity. In neutrophils from different volunteers, glucose inhibited uptake and accumulation of ascorbic acid by both transport activities 3-9-fold. The mechanism of inhibition was different for each transport activity: inhibition of the high affinity transport activity was noncompetitive, while inhibition of the low affinity activity was competitive. Glucose-induced inhibition of both ascorbic acid transport activities occurred in neutrophils of all donors tested and was fully reversible. Although the mechanism of ascorbic acid accumulation appeared to be different than that for glucose transport, other monosaccharides and glucose transport inhibitors also inhibited ascorbic acid accumulation. These are the first data to suggest that ascorbic acid accumulation in neutrophils can be regulated by compounds of similar structure.
Washko
P
P
Laboratory of Cell Biology and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Levine
M
M
D000328:Adult; D001205:Ascorbic Acid / Q000097:blood*; D001692:Biological Transport / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D003572:Cytochalasins / Q000494:pharmacology; D005459:Fluorides; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009005:Monosaccharides / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010693:Phloretin / Q000494:pharmacology; D010695:Phlorhizin / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D017680:Potassium Compounds; D013997:Time Factors
D003572:Cytochalasins; D009005:Monosaccharides; D017680:Potassium Compounds; D005576:Colforsin; C033320:potassium fluoride; D010695:Phlorhizin; D005947:Glucose; D001205:Ascorbic Acid; D005459:Fluorides; D011188:Potassium; D010693:Phloretin