Gentamicin causes endocytosis of Na/Pi cotransporter protein (NaPi-2).

Gentamicin causes endocytosis of Na/Pi cotransporter protein (NaPi-2). Background Renal toxicity is a major side-effect of aminoglycoside antibiotics and is characterized by an early impairment in proximal tubular function. In a previous study, we have shown that gentamicin administration to the rat causes an early impairment in sodium gradient-dependent phosphate (Na/Pi) cotransport activity. The purpose of our current study was to determine the molecular mechanisms of the impairment in Na/Pi cotransport activity, specifically the role of the proximal tubular type II Na/Pi cotransporter. Methods Rats were treated for one, two, and three days with two daily injections of 30 mg/kg body weight gentamicin or the vehicle. Results Gentamicin caused a progressive decrease in superficial cortical apical brush-border membrane (SC-BBM) Na/Pi cotransporter activity (856 ± 93 in control vs. 545 ± 87 pmol/mg BBM protein in 3-day gentamicin, P Conclusion We conclude that gentamicin inhibits Na/Pi cotransport activity by causing a decrease in the expression of the type II Na/Pi cotransport protein at the level of the proximal tubular apical BBM and that inhibition of Na/Pi cotransport activity is most likely mediated by post-transcriptional mechanisms.