INTERACTIONS OF NEOMYCIN AND CALCIUM IN SYNAPTOSOMAL MEMBRANES AND POLYPHOSPHOINOSITIDE MONOLAYERS

Neomycin and related aminoglycosidic antibiotics displace Ca from synaptosomes of guinea pig cerebral cortex and from preparations of phosphatidylinositol diphosphate. At low drug concentrations inhibition of synaptosomal Ca binding is competitive (Ki = 4 .cntdot. 10-5 M), at high concentrations it is non-competitive (Ki = 4 .cntdot. 10-4 M). Monomolecular films of phosphatidylinositol diphosphate are contracted by low concentrations of neomycin in the subphase and are expanded at high concentrations. This expansion persists even at the collapse pressure indicating a strong interaction between the drug and the lipid. [It remains to be established how the in vitro effects on Ca binding and on polyphosphoinositides relate to each other and to the in vivo toxicity of neomycin.].