Humes H D, Weinberg J M
J Lab Clin Med. 1983 Mar;101(3):472-8.
Early gentamicin nephrotoxicity is characterized by a variety of renal transport abnormalities, including polyuria secondary to nephrogenic diabetes insipidus. To investigate whether gentamicin directly interferes with cellular mechanisms responsible for ADH responsivity as a possible contributing factor in this tubular transport alteration, the effect of gentamicin on ADH-stimulated water flow was examined in vitro in the toad urinary bladder. Gentamicin decreased ADH-stimulated osmotic water flow in a dose-dependent manner, with a threshold effect at approximately 0.5 mM. This inhibitory effect occurred only in response to submaximal concentrations of ADH, was reversible, and was preventable with Mg++. Additionally, gentamicin reduced theophylline-stimulated osmotic water flow but had no effect on cyclic AMP-induced water flow. These effects are consistent with a direct gentamicin-related decrease in ADH-responsive adenylate cyclase activity and suggest a mechanism that may contribute to the nephrogenic diabetes insipidus characteristic of early gentamicin nephrotoxicity and the nonoliguric acute renal failure that is a late toxic event occurring with the use of this antibiotic.
早期庆大霉素肾毒性的特征是多种肾脏转运异常，包括继发于肾性尿崩症的多尿。为了研究庆大霉素是否直接干扰负责抗利尿激素（ADH）反应性的细胞机制，这可能是这种肾小管转运改变的一个促成因素，在蟾蜍膀胱中体外研究了庆大霉素对ADH刺激的水流量的影响。庆大霉素以剂量依赖的方式降低ADH刺激的渗透水流量，在约0.5 mM时具有阈值效应。这种抑制作用仅在对亚最大浓度的ADH作出反应时出现，是可逆的，并且可以用镁离子预防。此外，庆大霉素降低了茶碱刺激的渗透水流量，但对环磷酸腺苷（cAMP）诱导的水流量没有影响。这些效应与庆大霉素相关的ADH反应性腺苷酸环化酶活性直接降低一致，并提示了一种机制，该机制可能导致早期庆大霉素肾毒性的肾性尿崩症特征以及使用这种抗生素时发生的非少尿型急性肾衰竭这一晚期毒性事件。
