Gil F Z, Malnic G
Department of Physiology, Escola Paulita de Medicina, São Paulo, Brasil.
Pflugers Arch. 1989 Jan;413(3):280-6. doi: 10.1007/BF00583542.
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.
两性霉素B是一种已知可在生物细胞膜中诱导阳离子选择性孔形成的多烯抗生素，通过腹腔注射给予大鼠（10mg/kg，持续21 - 26天）或添加到管腔灌流液中（2×10⁻⁵M）。用双管锑/参比微电极在皮质远曲小管中研究了用碱性或酸性磷酸盐林格液灌流后肾小管酸化和碱化的动力学。早期和晚期远曲小管节段的静息pH均升高。酸化和碱化半衰期从15 - 18秒显著缩短至6 - 8秒，这一数值与近端小管中的数值相似。两性霉素B处理后，净氢离子分泌速率以及氢离子反向通量大约增加了一倍。在用磷酸盐林格液灌流管腔和肾小管周围毛细血管期间测量的远曲小管上皮细胞的表观氢离子通透性在早期和晚期节段均增加了一倍。这些数据表明，两性霉素B产生远端酸化缺陷，通过增加氢离子反向通量而不降低净氢离子分泌速率，损害正常跨上皮pH梯度的形成。
