Gentamicin nephrotoxicity. II. Plasma membrane changes.

Abstract Following acute exposure (1.5 hr) to a single injection of 100 mg/kg body weight gentamicin, brush border and basolateral membranes from rat renal cortex were isolated. A number of significant alterations were found in basolateral membranes from treated animals: (1) 48% inhibition of Na + , K + -ATPase, (2) inhibition of basal (50%) and NaF-stimulated (77%) adenylate cyclase, (3) 38% decrease in calcium binding, and (4) 19% reduction in calcium content. In basolateral and brush border membranes the transport of the organic cation, N 1 -methylnicotinamide (NMN), was depressed approximately 30%. By using [ 3 H]gentamicin the drug was found on both membranes. The role of Na + , K + -ATPase, adenylate cyclase, and calcium in a variety of membrane functions suggests that basolateral membrane changes may be important in the pathogenesis of gentamicin nephrotoxicity.