Gentamicin이 적혈구막을 통한 Na⁺ 이동에 미치는 영향

Effect of Gentamicin on Sodium Transport in Human Erythrocytes

Gentamicin (GM) is a polybasic, aminoglycoside antibiotic used frequently for the treatment of serious gram-negative infections. The major limiting factors in the clinical use of GM as well as other aminoglycoside antibiotics are their nephrotoxicity and ototoxicity. The primary mechanism of cell injury in aminoglycoside toxicity appears to be the disruption of normal membrane function and the inhibition of Na⁺-K⁺ ATPase activity. There are both indirect and direct evidences which suggests that the effect of aminoglycoside antibiotics on Na⁺-K⁺ ATPase may explain, or contribute to, their toxicity. It has been shown that aminoglycoside reduce total ATPase activity (Kaku et al., 1973) and Na⁺-K⁺ ATPase activity (linuma et al., 1967) in the stria vascularis and spiral ligament of the guinea-pig cochlea. Lipsky and Lietman (1980) reported that aminoglycoside antibitoics inhibited the activity of Na⁺-K⁺ ATPase in microsomal fractions of the cortex and medulla of the guinea-pig kidney, isolated rat renal tubule and human erythrocyte ghosts. The present invstigation was undertaken to elucidate the mechanism of GM on human erythrocytes by examining its effect on Na⁺-K⁺ ATPase activity, actives sodium and potassium transport across red blood cell and ³H-ouabain binding to red blood cell membranes. The results obtained are summarized as follows: 1) CM inhibited significantly both the activity of total ATPase and Na⁺-K⁺ ATPase at all concentrations tested. 2) GM inhibited active ²²H-ouabain efflux across red blood cell. When ouabain is present, the rate of ²²H-ouabain efflux was completely inhibited. When both GM and ouabain were added, the inhibitory effect of active ²²H-ouabain efflux was more pronounced. 3) Active ⁸⁶H-ouabain influx was inhibited significantly by GM. In the presence of ouabain, the rate of ⁸⁶H-ouabain influx is markedly inhibited. But ⁸⁶H-ouabain influx is not appreciably altered by the presence of both GM and ouabain. 4) In the presence of GM, ³H-ouabain binding to red blood cell membrane increased. From the above results, it may be concluded that the inhibition of active sodium and potassium transport across red blood cell by gentamicin appears to be due to the inhibition of Na⁺-K⁺ ATPase activity and an increase in ouabain binding to red blood cell membranes.