[Hearing loss caused by aminoglycoside antibiotics: affect on the membrane component PIP2 in outer hair cells as the mechanism of action].
Experiments with live isolated outer hair cells are described that provide an explanation of the toxic mechanism of aminoglycoside antibiotics. Outer hair cells were isolated from the guinea pig cochlea by microsurgery and maintained in artificial perilymph. The presence of the membrane lipid PIP2 (phosphatidylinositol bisphosphate) and other components of the phosphoinositide cycle was demonstrated through their labeling with radioactive phosphate. The lipids play a key role in the function of outer hair cells as part of a second messenger and amplification system that controls the motility of these cells. Furthermore, it was shown that the ototoxic aminoglycoside gentamicin has a selective and extremely high binding affinity to PIP2. The specific toxicity of aminoglycoside antibiotics is explained by the inhibition of the function of PIP2.
D000617:Aminoglycosides / Q000633:toxicity*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001665:Binding Sites; D002478:Cells, Cultured; D005839:Gentamicins / Q000378:metabolism / Q000633:toxicity; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects*; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced*; D008563:Membrane Lipids / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D005839:Gentamicins; D008563:Membrane Lipids; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols
Hörverlust durch Aminoglykosid Antibiotika: Angriff am Membranbaustein PIP2 in äusseren Haarzellen als Wirkungsmechanismus.