Haemonchus contortus:: HcGluCla expressed in Xenopus oocytes forms a glutamate-gated ion channel that is activated by ibotenate and the antiparasitic drug ivermectin
Haemonchus contortus:: HcGluCla expressed in Xenopus oocytes forms a glutamate-gated ion channel that is activated by ibotenate and the antiparasitic drug ivermectin
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DOI：
10.1016/s0166-6851(03)00102-6
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发表时间：
2003-06-01
影响因子：
1.5
通讯作者：
Beech, RN
中科院分区：
文献类型：
--
作者：
Forrester, SG;Prichard, RK;Beech, RN
离子通道是许多药物的靶标，包括杀虫剂和驱虫剂，如伊维菌素（IVM）和莫昔克丁（MOX）。IVM已显示激活来自自由生活的线虫秀丽隐杆线虫的谷氨酸门控氯离子通道（GluCl）。捻转血矛线虫是一种寄生线虫，也对IVM极其敏感。H. contortus到IVM可能是这样一个事实的结果，像C。elegans，H.扭体也表达GluCl。目的：探讨体外培养对H.我们已经表达了来自这种寄生虫的GluCl（H.在非洲爪蟾卵母细胞中的谷氨酸门控氯离子通道（HcGluCla）。在卵母细胞中表达的HcGluCla形成对谷氨酸和鹅膏蕈氨酸以及驱虫剂IVM和MOX响应的同源通道。对谷氨酸和鹅膏蕈氨酸的响应是快速作用和可逆的，而对IVM和MOX的响应是基本上不可逆的较慢激活通道。这些结果表明，IVM毒性H。扭转是其不可逆激活GluCl s的结果。(C)2003 Elsevier Science B.V.保留所有权利。
Ion channels are targets for many drugs including insecticides and anthelminthic agents such as ivermectin (IVM) and moxidectin (MOX). IVM has been shown to activate glutamate-gated chloride channels (GluCls) from the free-living nematode, Caenorhabditis elegans. Haemonchus contortus is a parasitic nematode that is also extremely sensitive to IVM. The high sensitivity of H. contortus to IVM is probably the result of the fact that, like C. elegans, H. contortus also express GluCls. To investigate the potential physiological response to IVM in H. contortus we have expressed a GluCl from this parasite (H. contortus glutamate-gated chloride channel, HcGluCla) in Xenopus oocytes. HcGluCla expressed in oocytes formed a homomeric channel that responded to glutamate and ibotenate as well as the anthelmintics IVM and MOX The response to glutamate and ibotenate was fast acting and reversible whereas the response to IVM and MOX was a slower activating channel that was essentially irreversible. These results suggest that IVM toxicity in H. contortus is the result of its irreversible activation of GluCls. (C) 2003 Elsevier Science B.V. All rights reserved.