Rybak L P, Whitworth C
Department of Surgery, SIU School of Medicine 62794-9230.
Am J Otolaryngol. 1988 Sep-Oct;9(5):238-43. doi: 10.1016/s0196-0709(88)80033-4.
Endocochlear potential (EP) and eighth nerve action potential (AP) were measured in chinchillas. We investigated the interaction of quinine with the loop diuretics furosemide and ethacrynic acid to determine whether the cochlear effects of these agents are attenuated by pretreatment with quinine. Animals were injected with either furosemide, 25 mg/kg intravenously (IV), or ethacrynic acid, 15 mg/kg IV. Control animals injected without pretreatment were found to have a large decrease in EP, with a decrease of compound action potentials (CAP) amplitude and an elevation of CAP threshold. Animals pretreated with quinine, 25 mg/kg, were found to have a significantly smaller reduction of EP and CAP amplitude following injection of either diuretic. No significant differences in urine volumes were noted between experimental and control groups. Quinine is known to cause nonspecific changes in the membranes of epithelial cells, which may cause alterations of the transport of organic anions by such tissues. Such an effect on epithelial cells in the cochlea may cause reduced uptake of loop diuretics in this organ, resulting in reduced toxicity.
在栗鼠身上测量了内淋巴电位(EP)和第八对脑神经动作电位(AP)。我们研究了奎宁与袢利尿剂呋塞米和依他尼酸之间的相互作用,以确定这些药物的耳蜗效应是否会因预先使用奎宁而减弱。给动物静脉注射25mg/kg呋塞米或15mg/kg依他尼酸。未进行预处理而注射的对照动物被发现EP大幅下降,复合动作电位(CAP)幅度降低,CAP阈值升高。预先注射25mg/kg奎宁的动物在注射任一利尿剂后,EP和CAP幅度的降低明显较小。实验组和对照组之间的尿量没有显著差异。已知奎宁会引起上皮细胞膜的非特异性变化,这可能导致此类组织对有机阴离子转运的改变。对耳蜗上皮细胞的这种作用可能会导致该器官对袢利尿剂的摄取减少,从而降低毒性。