Interaction of Neomycin with Phosphoinositide Metabolism in Guinea Pig Inner Ear and Brain Tissues

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Abstract
Phospholipids of guinea pig inner ear tissues were labeled in vivo by perfusing the perilymphatic spaces with 32P-labeled inorganic phosphate. The most highly labeled lipids obtained after a 45 min incubation time were phosphatidylinositol phosphate and phosphatidylinositol diphosphate. 32P-incorporation into the latter in the Organ of Corti was significantly decreased in guinea pigs previously treated with neomycin (100 mg/kg body weight) for 21 days. In in vitro experiments with subcellular fractions of guinea pig cerebral cortex, neomycin (10−4 M) altered the labeling of the polyphosphoinositides from γ−32P-ATP and inhibited their hydrolysis. It is suggested that neomycin toxicity is mediated by an inhibition of polyphosphoinositide turnover.