Selective inhibition by ethanol of the type 1 facilitative glucose transporter (GLUT1)

Ethanol appears to modulate the function of selective mammalian receptors and transporters by interacting with highly specific membrane protein sites. Of the multiple types of nucleoside transporters known to be present in mammalian cells, we observed that ethanol inhibits only one class of facilitative nucleoside transporters, that inhibited by nitrobenzylmercaptopurine riboside. Because there are biochemical similarities between facilitative glucose transporters and nitrobenzylmercaptopurine riboside-sensitive nucleoside transporters, we tested whether ethanol might selectively inhibit a unique class of facilitative glucose transporters. We report here that ethanol inhibits hexose uptake in human lymphocytes and several cell lines expressing the ubiquitous facilitative type 1 glucose transporter (GLUT1). Ethanol inhibition of hexose uptake by GLUT1 is independent of ethanol inhibition of facilitative nucleoside transport. We also determined the ethanol sensitivity of various cloned human facilitative glucose transporters expressed in Chinese hamster ovary cells and we found that ethanol inhibits hexose uptake by GLUT1 but not uptake by GLUT3 or GLUT4 transporters. Our results suggest that a protein motif or motifs present in the GLUT1 amino acid sequence but absent in GLUT3 or GLUT4 proteins may confer ethanol sensitivity.