Lipsky J J, Lietman P S
J Pharmacol Exp Ther. 1982 Feb;220(2):287-92.
Aminoglycosides are able to inhibit phosphatidylinositol phospholipase C activity in a soluble fraction of rat renal tissue. The Km of the enzyme with respect to phosphatidylinositol is 0.53 mM and Vmax was 0.671 mumol of phosphatidylinositol cleaved per hr per mg of protein. The enzyme is calcium activated and inhibited by ethylene glycol bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid. Streptomycin, amikacin, kanamycin, tobramycin, gentamicin and neomycin inhibit enzyme activity in the same rank order as their ability to produce nephrotoxicity. The 50% inhibitory concentrations ranged from 0.03 mM for neomycin to 0.38 mM for streptomycin. Lineweaver Burk plots indicate competitive inhibition with a possible relation to the calcium activation. It is possible that aminoglycosides may inhibit phosphatidylinositol phospholipase C in vivo and that this inhibition may be related to the nephrotoxicity of aminoglycosides.
氨基糖苷类能够抑制大鼠肾组织可溶性部分中的磷脂酰肌醇磷脂酶C活性。该酶对磷脂酰肌醇的米氏常数（Km）为0.53 mM，最大反应速度（Vmax）为每小时每毫克蛋白质裂解0.671 μmol磷脂酰肌醇。该酶受钙激活，并被乙二醇双（β-氨基乙醚）-N，N'-四乙酸抑制。链霉素、阿米卡星、卡那霉素、妥布霉素、庆大霉素和新霉素抑制酶活性的顺序与其产生肾毒性的能力相同。50%抑制浓度范围从新霉素的0.03 mM到链霉素的0.38 mM。Lineweaver Burk图表明为竞争性抑制，可能与钙激活有关。氨基糖苷类可能在体内抑制磷脂酰肌醇磷脂酶C，并且这种抑制可能与氨基糖苷类的肾毒性有关。
