Marche P, Olier B, Girard A, Morin J P
Pathol Biol (Paris). 1985 May;33(5):373-6.
Phosphoinositides play a major role in the interaction between aminoglycosides and renal epithelial cells. We therefore investigated both in vivo and in vitro, in isolated proximal tubules and in various parts of the rabbit kidney, the influence of neomycin, gentamicin and amikacin on the phosphoinositide metabolism. This was carried out by measuring the 32p incorporation into phosphatidylinositol 4,5-bisphosphates (PI-P2) and phosphatidylinositol 4-phosphates (PI-P). In aminoglycoside-treated animals, compared to untreated controls, the 32 p-PI-P2 and 32p-PI-P levels were decreased and increased respectively in proximal tubules and in cortical areas but these levels were unchanged in papilla and in medulla. Similar variations could be obtained after exogenous addition of aminoglycosides. PI-P2 is a key membrane component in the regulation of both the Ca2+ transport and the intracellular Ca2+ mobilization. Thus, the aminoglycoside-induced modifications of the phosphoinositide metabolism may be considered as a primary event in the drug toxicity which may result from alterations in the cell calcium homeostasis.
磷酸肌醇在氨基糖苷类药物与肾上皮细胞的相互作用中起主要作用。因此，我们在体内和体外，对分离的近端小管和兔肾的各个部位，研究了新霉素、庆大霉素和阿米卡星对磷酸肌醇代谢的影响。这是通过测量32P掺入磷脂酰肌醇4,5-二磷酸（PI-P2）和磷脂酰肌醇4-磷酸（PI-P）来进行的。在氨基糖苷类药物处理的动物中，与未处理的对照组相比，近端小管和皮质区域的32P-PI-P2水平降低，32P-PI-P水平升高，但乳头和髓质中的这些水平没有变化。外源添加氨基糖苷类药物后也可得到类似的变化。PI-P2是调节Ca2+转运和细胞内Ca2+动员的关键膜成分。因此，氨基糖苷类药物引起的磷酸肌醇代谢改变可能被认为是药物毒性的主要事件，这可能是由于细胞钙稳态的改变所致。
