Gentamicin이 막성와우 및 신장근위세뇨관 Na-K-ATPase 활성도에 미치는 영향

Effects of gentamicin on the Na⁺, K⁺-activated adenosine triphosphatase (Na-K-ATPase) activities of rabbit membranous cochlear homogenates and renal cortical basolateral membranes were studies to investigate mechanisms of gentamicin-induced ototoxicity and nephrotoxicity.

From normal adult rabbits anesthetized with pentobarbital sodium, membranous cochleae were dissected out under a stereomicroscope and homogenized. Renal cortical basolateral membranes were isolated by Percoli gradient centrifugation. The Na-K-ATPase activity was determined by measuring inorganic phosphate liberated during incubation of tissue homogenates or membrane fractions with ATP at 37°C. The enzyme activity was determined in the presence and absence of gentamicin in the preincubation and incubation media. The period of preincubation was 60 minutes and that of incubation was 20 minutes(renal ATPase) or 30 minutesCcochlear ATPase).

Treatment of cochlear homogenates with ImM gentamicin resulted in a significant reduction of Na-K-ATPase activity. Likewise, in renal cortical basolateral membrane fractions, the enzyme activity was significantly attenuated by 1 ∼lOmM gentamicin treatment, the effect being proportional to the concentration of the antibiotic. Kinetic analysis indicated that the reduction of renal Na-K-ATPase activity by gentamicin was due to an increase in Km with no change in Vmax.

These results indicate that both in the cochlea and renal proximal tubule, gentamicin inhibits the active Na⁺ and K⁺ transport process by changing the substrate affinity of the Na- K-ATPase system, which may lead to iterations of cochlear and renal function.