Altered drug resistance and recovery from paralysis in Drosophila melanogaster with a deficient histamine-gated chloride channel

Altered drug resistance and recovery from paralysis in Drosophila melanogaster with a deficient histamine-gated chloride channel
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DOI:
10.1080/01677060216293
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发表时间:
2002-10-01
影响因子:
1.9
通讯作者:
Semenov, EP
Semenov, EP
中科院分区:
医学4区
文献类型:
--
作者:
Iovchev, M;Kodrov, P;Semenov, EP

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最近对编码黑腹果蝇组胺门控氯通道亚单位的两个基因的鉴定证实,组胺是果蝇的主要神经递质。其中一个克隆的基因hclA(同义词:HisCl-alpha1;HisCl2)对应于ort(或暂时性的),其突变会影响果蝇视觉系统中的突触传递。我们在携带ort(1)等位基因的突变体中发现了hclA的基因组和RNA拷贝的突变(零突变)。这与在突变品系中观察到的新表型有关。我们发现,与俄勒冈州R野生型动物相比,ORT(1)成虫和三龄幼虫对阿维菌素神经毒素都过敏。另一方面,突变使雄性和雌性成年果蝇都对乙醚治疗产生了更强的抵抗力,而且动物在乙醚麻醉后的瘫痪恢复时间以及机械休克后的瘫痪恢复时间都大大延长,bang敏感性测试显示。总之,我们的数据提供了直接的证据,表明在体内,含有HCLA亚单位的受体在阿维菌素的神经毒性作用中具有独特的作用。它们还为乙醚麻醉的反应功能提供了新的证据,而且,HCLA的功能并不局限于视觉系统。
The recent identification and characterization of two genes, encoding histamine-gated chloride channel subunits from Drosophila melanogaster, has confirmed that histamine is a major neurotransmitter in the fruitfly. One of the cloned genes, hclA (synonyms: HisCl-alpha1; HisCl2), corresponds to ort (ora transientless), mutations in which affect synaptic transmission in the Drosophila visual system. We identified a mutational change (a null mutation) in the genomic and RNA copies of hclA derived from mutants carrying the ort(1) allele. This correlates with new phenotypes observed in the mutant strain., We found hypersensitivity to the avermectin neurotoxins in both the ort(1) adult flies and third instar larvae compared to Oregon R wild-type animals. On the other hand, the mutation makes both male and female adult flies more resistant to treatment with diethyl ether, and the animals show substantially prolonged recovery from paralysis after diethylether anaesthesia, as well as from paralysis after mechanical shock, as revealed by the bang sensitivity test. Altogether, our data give direct evidence that in vivo a HCLA subunit-containing receptor has a distinct role in the neurotoxic action of the avermectins. They also provide new evidence for a function in the response to diethylether anaesthesia and, moreover, that HCLA function is not limited to the visual system.