EFFECTS OF OTOTOXINS ON QUINUCLIDINYL BENZYLATE BINDING IN THE RAT COCHLEA

Ototoxins inhibit the muscarinic receptor-activated inositol phosphate synthesis in the rat cochlea. In order to study this inhibitory mecha nism, we investigated the effects of the ototoxins ethacrynate, cispla tin, HgCl2 and neomycin on [H-3]quinuclidinyl benzylate binding to mus carinic receptors in adult and 12-day-old rat cochleas. The results ar e similar whatever the age: at concentrations that inhibit the inosito l phosphate synthesis, ethacrynate is without effect. Neomycin only re duces [H-3]quinuclidinyl benzylate binding at concentrations in the mi llimolar range. Cisplatin and HgCl2 block the binding in a dose-depend ent way. These results suggest that the block of the transduction syst em by cisplatin and HgCl2 is due to direct interactions with muscarini c binding sites. Moreover, considering these data together with previo us results, ethacrynate and neomycin may affect the phosphoinositide s ignalling pathway at targets including phosphoinositides and G protein s.