1. Effects of ototoxins on quinuclidinyl benzylate binding in the rat cochlea
- Author
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Myriam Planche, Rémy Pujol, Sylvain Bartolami, Mécanismes moléculaires dans les démences neurodégénératives (MMDN), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)
- Subjects
G protein ,Neurotoxins ,In Vitro Techniques ,03 medical and health sciences ,0302 clinical medicine ,Ototoxicity ,Muscarinic acetylcholine receptor ,medicine ,Animals ,Rats, Wistar ,Binding site ,Hearing Disorders ,030304 developmental biology ,Acetylcholine receptor ,0303 health sciences ,Membranes ,Chemistry ,General Neuroscience ,Muscarinic receptor ,Neomycin ,medicine.disease ,Receptors, Muscarinic ,Cochlea ,Rats ,Quinuclidinyl Benzilate ,Kinetics ,Mercuric chloride ,Ethacrynate ,Mechanism of action ,Biochemistry ,Second messenger system ,Biophysics ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Cisplatin ,medicine.symptom ,030217 neurology & neurosurgery ,Signal Transduction ,[3H]Quinuclidinyl benzylate ,medicine.drug - Abstract
International audience; Ototoxins inhibit the muscarinic receptor-activated inositol phosphate synthesis in the rat cochlea. In order to study this inhibitory mechanism, we investigated the effects of the ototoxins ethacrynate, cisplatin, HgCI2 and neomycin on [3H]quinuclidinyl benzylate binding to muscarinic receptors in adult and 12-day-old rat cochleas. The results are similar whatever the age: at concentrations that inhibit the inositol phosphate synthesis, ethacrynate is without effect. Neomycin only reduces [3H]quinuclidinyl benzylate binding at concentrations in the millimolar range. Cisplatin and HgCI2 block the binding in a dose-dependent way. These results suggest that the block of the transduction system by cisplatin and HgCI2 is due to direct interactions with muscarinic binding sites. Moreover, considering these data together with previous results, ethacrynate and neomycin may affect the phosphoinositide signalling pathway at targets including phosphoinositides and G proteins.
- Published
- 1994
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