SELECTIVE-INHIBITION BY ETHANOL OF THE TYPE-1 FACILITATIVE GLUCOSE-TRANSPORTER (GLUT1)

Ethanol appears to modulate the function of selective mammalian recept ors and transporters by interacting with highly specific membrane prot ein sites. Of the multiple types of nucleoside transporters known to b e present in mammalian cells, we observed that ethanol inhibits only o ne class of facilitative nucleoside transporters, that inhibited by ni trobenzylmercaptopurine riboside. Because there are biochemical simila rities between facilitative glucose transporters and nitrobenzylmercap topurine riboside-sensitive nucleoside transporters, we tested whether ethanol might selectively inhibit a unique class of facilitative gluc ose transporters. We report here that ethanol inhibits hexose uptake i n human lymphocytes and several cell lines expressing the ubiquitous f acilitative type 1 glucose transporter (GLUT1). Ethanol inhibition of hexose uptake by GLUT1 is independent of ethanol inhibition of facilit ative nucleoside transport. We also determined the ethanol sensitivity of various cloned human facilitative glucose transporters expressed i n Chinese hamster ovary cells and we found that ethanol inhibits hexos e uptake by GLUT1 but not uptake by GLUT3 or GLUT4 transporters. Our r esults suggest that a protein motif or motifs present in the GLUT1 ami no acid sequence but absent in GLUT3 or GLUT4 proteins may confer etha nol sensitivity.