INHIBITION BY NEOMYCIN OF POLYPHOSPHOINOSITIDE TURNOVER IN SUBCELLULAR FRACTIONS OF GUINEA‐PIG CEREBRAL CORTEX IN VITRO

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Abstract
The addition of 10-5 M to 10-3 M neomycin to incubations of subcellular fractions of guinea pig cerebral cortex increased the labeling of phosphatidylinositol phosphate and decreased the labeling of phosphatidylinositol diphosphate by [.gamma.-32P]ATP. The effect was observed in all subcellular fractions tested and depended on the cationic form of the antibiotic. Similar effects on lipid labeling were exerted by related aminoglycosidic antibiotics, by neamine, spermine and poly-L-lysine. Other neomycin fragments, antibiotics, local anesthetics or small polyamines were ineffective. Neomycin also inhibited the enzymatic hydrolysis of 32P-polyphosphoinositides. The addition of the drug to aqueous dispersions of these lipids increased the turbidity and lowered the pH of the suspensions. The effects of neomycin on polyphosphoinositide metabolism possibly result from the formation of an ionic complex between the lipids and the antibiotic. [The results are discussed in relation to neomycin ototoxicity.].