دورية أكاديمية
Sulphhydryl-modifying Reagents Alter Ototoxin Block of M uscarinic Receptor-lin ked Phosphoinositide Turnover in the Cochlea
| العنوان: | Sulphhydryl-modifying Reagents Alter Ototoxin Block of M uscarinic Receptor-lin ked Phosphoinositide Turnover in the Cochlea |
|---|---|
| المؤلفون: | Bartolami, Sylvain, Planche, Myriarn, Pujol, Rémy |
| المساهمون: | Neurobiologie de l'audition-plasticité synaptique, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| المصدر: | ISSN: 0953-816X. |
| بيانات النشر: | HAL CCSD Wiley |
| سنة النشر: | 1993 |
| المجموعة: | Inserm: HAL (Institut national de la santé et de la recherche médicale) |
| مصطلحات موضوعية: | rat, N-ethylmaleirnide, cadmium, ototoxic drugs, inositol phosphates, muscarinic receptors, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] |
| الوصف: | International audience ; In the 12-day-old rat cochlea, the synthesis of inositol phosphates (IPS) can be activated via M3 cholinoceptors. This stimulation is blocked by ototoxins (mercury, ethacrynate, cisplatin, neomycin), drugs with side effects that lead to damage of hair cells and strial cells. As these toxic effects can be reversed in vivo by thiol molecules, we investigated whether modifications of thiol compounds could be involved in ototoxin-induced inhibition of the IP turnover in the cochlea. For this purpose, we assessed whether the sulphhydryl-modifying reagents N-ethylmaleimide and cadmium modify the carbachol-stimulated formation of IPS in the 12-day-old rat cochlea. Both molecules inhibit the carbachol effect on a dose-dependent way without altering the basal metabolism of IPS. As cadmium may block some calcium channels, the effect of verapamil, another calcium channel antagonist, was tested. Verapamil (1-50 pM) does not alter carbachol-evoked IP formation, suggesting that the inhibitory effect of cadmium is not due to a calcium influx block. Binding experiments with the muscarinic ligand quinuclidinyl benzylate (QNB) showed that the sulphhydryl-modifying reagents do not displace QNB from binding sites. Combining ototoxins and reagents shows that N-ethylmaleimide acts synergistically with all ototoxins but ethacrynate while cadmium does so only with mercury. Both N-ethylmaleimide and cadmium have additive effects with ethacrynate. As a supplement, disulphide bond-modifying agents do not alter the carbachol-enhanced metabolism of IPS. These results suggest that molecules having thiol-modifying properties inhibit the carbachol-induced turnover of IPS without acting at the muscarinic sites. Since thiol modifiers and ethacrynate share similar features in both QNB binding and IP response it is hypothesized that they strike common targets, possibly G proteins. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | hal-02163275; https://hal.science/hal-02163275Test; https://hal.science/hal-02163275/documentTest; https://hal.science/hal-02163275/file/Bartolami_et_al-1993-European_Journal_of_Neuroscience.pdfTest |
| الإتاحة: | https://hal.science/hal-02163275Test https://hal.science/hal-02163275/documentTest https://hal.science/hal-02163275/file/Bartolami_et_al-1993-European_Journal_of_Neuroscience.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.CB8296D8 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |