Inhibition of inner ear ornithine decarboxylase by neomycin in-vitro.
We quantitated the activity of ornithine decarboxylase (ODC) in homogenates and subcellular fractions of inner ear tissues from the rat and guinea pig and demonstrate inhibition of cochlear ODC by the aminoglycoside neomycin. Subcellular fractionation showed the enzyme associated with the post-mitochondrial supernatant fraction in each of the tissues: Specific activities of ODC, defined as alpha-difluoromethylornithine (DFMO)-sensitive decarboxylation of ornithine, in the supernatant fractions of combined inner ear tissues were: guinea pig = 44 +/- 4 pmoles CO2 produced/hour/mg protein, and rat = 133 +/- 30. In the guinea pig, supernatant fractions of the lateral wall tissues (stria vascularis and spiral ligament) had specific activities of 62 +/- 25, those of the organ of Corti (plus VIIIth nerve) 64 +/- 41. The ototoxic aminoglycoside neomycin produced a dose-dependent inhibition of ODC with half-maximal inhibition observed at 50 microM drug and almost complete inhibition at 100 microM. This is the first report of the presence of ODC in the inner ear and its inhibition by neomycin. Since both the ODC-inhibitors, DFMO and neomycin, can cause hearing loss in patients and experimental animals it is suggested that inhibition of ODC may be an important factor in the ototoxicity of these drugs.
D000818:Animals; D003051:Cochlea / Q000201:enzymology*; D000518:Eflornithine / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D009355:Neomycin / Q000494:pharmacology*; D009928:Organ Specificity; D065108:Ornithine Decarboxylase Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013347:Subcellular Fractions / Q000201:enzymology
D065108:Ornithine Decarboxylase Inhibitors; D009355:Neomycin; D000518:Eflornithine