Résumé
The ability of amikacin, neomycin, ethacrynate, mercuric chloride and cisplatin to alter the inositol phosphate (IP) signalling pathway was assessed in the 12-day-old rat cochlea, where the turnover of IPs is coupled to muscarinic receptors. This study was motivated by: (1) the demonstration of neomycin binding to phosphatidylinositol 4,Sbiphosphate, the precursor of IPs, and (2) the fact that ototoxic drugs induce some common symptoms in outer hair cells. At concentrations below 1 mM, none of the compounds changed the control 'H-IP formation. Mercuric chloride, cisplatin and ethacrynate inhibited the carbachol-induced formation of IPs in a dose-dependent manner with IC?,, values of 74, 340 and 430 /LM. respectively. The aminoglycosides were less efficient in reducing the carbachol-stimulated accumulation of IPs, since neither amikacin nor neomycin. both at 1 mM, had any significant effect. However. neomycin applied at 15 and 30 PM induced 29% and 43% of inhibition of the stimulated IP response. Finally, additive effects are obtained between some of the toxic drugs. The results suggest that a block of the IP transduction system, associated with the cholinergic efferent innervation of the organ of Corti, is a feature that may he involved in some types of ototoxicity. The inefficiency of aminoglycosides and the putative targets of the ototoxic agents are discussed.