Archives of oto-rhino-laryngology

, Volume 224, Issue 1–2, pp 129–134 | Cite as

Isolation of an aminoglycoside receptor from guinea pig inner ear tissues and kidney

  • Jochen Schacht
Article

Summary

Affinity chromatography was used to isolate aminoglycoside receptors from inner ear tissues and kidney. Neomycin was immobilized on glass beads and served as the stationary phase in column chromatography. Fractionation of an organic tissue extract on this matrix demonstrated two components with high affinity for neomycin: phosphatidyl inositol phosphate and phosphatidyl inositol diphosphate. The toxicity of aminoglycosides is explained on the basis of a drug-interaction with these lipids.

Key words

Aminoglycoside ototoxicity Neomycin Drug receptors Affinity chromatography Polyphosphoinositides 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Deguchi, T., Ishii, A., Tanaka, M.: Binding of aminoglycoside antibiotics to acidic mucopolysaccharides. J. Antibiot. 31, 150–155 (1978)Google Scholar
  2. Hauser, G., Eichberg, J.: Improved conditions for the preservation and extraction of polyphosphoinositides. Biochim. Biophys. Acta 326, 201–209 (1973)Google Scholar
  3. Hendrickson, H. S., Ballou, C. E.: Ion exchange chromatography of intact brain phosphoinositides on diethylaminoethyl cellulose by gradient salt elution in a mixed solvent system. J. Biol. Chem. 239, 1369–1373 (1964)Google Scholar
  4. Jarlstedt, J., Bagger-Sjöbäck, D.: Gentamicin-induced changes in RNA content in sensory and ganglionic cells in the hearing organ of the lizard Calotes Versicolor. Acta Otolaryngol. (Stockh.) 84, 361–369 (1977)Google Scholar
  5. Kai, M., Hawthorne, J. N.: Physiological significance of polyphosphoinositides in brain. Ann. N.Y. Acad. Sci. 165, 761–773 (1969)Google Scholar
  6. Lodhi, S., Weiner, N. D., Schacht, J.: Interactions of neomycin and calcium in synaptosomal membranes and polyphosphoinositide monolayers. Biochim. Biophys. Acta 426, 781–785 (1976)Google Scholar
  7. Orsulakova, A., Stockhorst, E., Schacht, J.: Effect of neomycin of phosphoinositide labeling and calcium binding in guinea pig inner ear tissues in vivo and in vitro. J. Neurochem. 26, 285–290 (1976)Google Scholar
  8. Pestka, S.: Inhibitors of ribosome functions. Annu. Rev. Biochem. 40, 697–710 (1971)Google Scholar
  9. Schacht, J.: Inhibition by neomycin of polyphosphoinositide turnover in subcelluar fractions of guinea pig cerebral cortex in vitro. J. Neurochem. 27, 1119–1124 (1976)Google Scholar
  10. Schacht, J.: Purification of polyphosphoinositides by chromatography on immobilized neomycin. J. Lipid Res. 19, 1063–1067 (1978)Google Scholar
  11. Schacht, J., Lodhi, S., Weiner, N. D.: Effects of neomycin on polyphosphoinositides in inner ear tissues and monomolecular films. In: Membrane Toxicity. Miller, M. W., Shamoo, A. E. (eds.), pp. 191–208. New York: Plenum Press 1977Google Scholar
  12. Schibeci, A., Schacht, J.: Action of neomycin on the metabolism of polyphosphoinositides in the guinea pig kidney. Biochem. Pharmacol. 26, 1769–1774 (1977)Google Scholar
  13. Stockhorst, E., Schacht, J.: Radioactive labeling of phospholipids and proteins by cochlear perfusion in the guinea pig and the effect of neomycin. Acta Otolaryngol. (Stockh.) 83, 401–409 (1977)Google Scholar
  14. Tachibana, M., Mizukoshi, O., Kuriyama, K.: Inhibitory effects of kanamycin on glycolysis in cochlea and kidney — possible involvement in the formation of oto- and nephrotoxicities. Biochem. Pharmacol. 25, 2297–2301 (1976)Google Scholar

Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • Jochen Schacht
    • 1
  1. 1.Kresge Hearing Research InstituteThe University of MichiganAnn ArborUSA

Personalised recommendations