Effect of amphotericin B on renal tubular acidification in the rat

Amphotericin B, a polyene antibiotic known to induce cation-selective pore formation in biological cell membranes, was given to rats by peritoneal injection (10 mg/kg for 21-26 days) or added to luminal perfusates (2 x 10(-5) M). Kinetics of tubular acidification and alkalinization after perfusion with alkaline or acid phosphate Ringer's solution was studied by means of double barrelled antimony/reference microelectrodes in cortical distal tubules. Stationary pH increased both in early and late distal segments. Acidification and alkalinization half-times decreased markedly from 15-18 s to 6-8 s, a value similar to that found in proximal tubule. Net H-ion secretion rates as well as H-ion back-flux approximately doubled after Amphotericin B. Apparent H-ion permeability of distal tubule epithelium measured during perfusion of lumen and peritubular capillaries with phosphate Ringer's solutions doubled both in early and late segments. These data show that amphotericin B produces a distal acidification defect which impairs formation of normal transepithelial pH gradients by increasing H-ion back-flux without reducing rates of net H-ion secretion.