Bartolami S, Planche M, Pujol R
Laboratoire de Neurobiologie de l'Audition, INSERM U254, CHU Saint Charles, Montpellier, France.
Neurosci Lett. 1994 Jun 20;174(2):169-72. doi: 10.1016/0304-3940(94)90013-2.
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, HgCl2 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 HgCl2 block the binding in a dose-dependent way. These results suggest that the block of the transduction system by cisplatin and HgCl2 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.
耳毒素可抑制大鼠耳蜗中由毒蕈碱受体激活的肌醇磷酸合成。为研究这种抑制机制，我们研究了耳毒素利尿酸、顺铂、氯化汞和新霉素对成年及12日龄大鼠耳蜗中[3H]喹核醇基苯甲酸酯与毒蕈碱受体结合的影响。无论年龄如何，结果相似：在抑制肌醇磷酸合成的浓度下，利尿酸无作用。新霉素仅在毫摩尔范围内的浓度下才会降低[3H]喹核醇基苯甲酸酯的结合。顺铂和氯化汞以剂量依赖方式阻断结合。这些结果表明，顺铂和氯化汞对转导系统的阻断是由于与毒蕈碱结合位点的直接相互作用。此外，综合这些数据和先前的结果来看，利尿酸和新霉素可能在包括磷脂酰肌醇和G蛋白在内的靶点上影响磷酸肌醇信号通路。
