Identification of an Ascaris G protein-coupled acetylcholine receptor with atypical muscarinic pharmacology.
Identification of an Ascaris G protein-coupled acetylcholine receptor with atypical muscarinic pharmacology.
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DOI：
10.1016/j.ijpara.2009.03.001
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发表时间：
2009-09
影响因子：
4
通讯作者：
Ribeiro P
中科院分区：
文献类型：
--
作者：
Kimber MJ;Sayegh L;El-Shehabi F;Song C;Zamanian M;Woods DJ;Day TA;Ribeiro P
乙酰胆碱（Acetylcholine，ACh）是线虫神经系统中的一种神经递质/神经调质，通过与配体门控离子通道（Ligand-gated ion channels，LGIC）和G蛋白偶联受体（G protein-coupled receptor，GPCRs）相互作用发挥作用。LGIC的结构、药理学和生理学重要性已经在模型线虫中得到了相当程度的阐明，包括作为驱虫药物靶标的寄生虫物种。然而，对线虫ACh GPCR（称为加尔斯（G蛋白连接ACh受体））的了解明显较少。已知的是来自自由生活的秀丽隐杆线虫，因为没有加尔斯的特征来自寄生物种。在这里，我们从猪胃肠道线虫猪蛔虫中克隆了一个推定的GAR，该GAR与C.线虫受体GAR-1。我们的GPCR，被称为AsGAR-1，是选择性剪接，并在蠕虫的头部和尾部表达，但不在背部或腹体壁肌肉，或产卵器。ACh以浓度依赖性方式激活AsGAR-1，但该受体不被其他小的神经递质激活。经典的毒蕈碱激动剂卡巴胆碱，槟榔碱，oxotremorine M和bethanechol也是AsGAR-1激动剂，但毛果芸香碱无效。乙酰胆碱对AsGAR-1的激活可被毒蕈碱阻断剂阿托品部分拮抗，但哌仑西平和东莨菪碱基本无效。还发现某些生物胺GPCR拮抗剂阻断AsGAR-1。我们的结论是，蛔虫具有G蛋白偶联的ACh受体，其结构与C. elegans，并且尽管它们与脊椎动物毒蕈碱受体具有一定的序列同源性，但它们的药理学是有害的毒蕈碱。
Acetylcholine (ACh) is a neurotransmitter/neuromodulator in the nematode nervous system and induces its effects through interaction with both ligand-gated ion channels (LGICs) and G protein-coupled receptors (GPCRs). The structure, pharmacology and physiological importance of LGICs have been appreciably elucidated in model nematodes, including parasitic species where they are targets for anthelmintic drugs. Significantly less, however, is understood about nematode ACh GPCRs, termed GARs (G protein-linked ACh receptors). What is known comes from the free-living Caenorhabditis elegans as no GARs have been characterized from parasitic species. Here we clone a putative GAR from the pig gastrointestinal nematode Ascaris suum with high structural homology to the C. elegans receptor GAR-1. Our GPCR, dubbed AsGAR-1, isalternatively spliced and expressed in the head and tail of adult worms but not in dorsal or ventralbody wall muscle, or the ovijector. ACh activated AsGAR-1 in a concentration-dependent manner but the receptor was not activated by other small neurotransmitters. The classical muscarinic agonists carbachol, arecoline, oxotremorine M and bethanechol were also AsGAR-1 agonists but pilocarpine was ineffective. AsGAR-1 activation by ACh was partially antagonized by the muscarinic blocker atropine but pirenzepine and scopolamine were largely ineffective. Certain biogenic amine GPCR antagonists were also found to block AsGAR-1. Our conclusion is that Ascaris possesses G protein-coupled ACh receptors that are homologous in structure to thosepresent in C. elegans, and that although they have some sequence homology to vertebrate muscarinic receptors, their pharmacology is atypically muscarinic.
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影响因子：
4.8
作者：
BURSTEIN, ES;SPALDING, TA;BRANN, MR
通讯作者：
BRANN, MR
DOI：
10.1111/j.1432-1033.1994.tb20050.x
发表时间：
1994-12-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
KAMEYAMA, K;HAGA, K;SADEE, W
通讯作者：
SADEE, W
DOI：
10.1254/jjp.43.277
发表时间：
1987-03-01
期刊：
JAPANESE JOURNAL OF PHARMACOLOGY
影响因子：
--
作者：
KUBO, N;SHIRAKAWA, O;TANAKA, C
通讯作者：
TANAKA, C
DOI：
10.1073/pnas.92.25.11642
发表时间：
1995-12-05
影响因子：
11.1
作者：
LIU, J;CONKLIN, BR;WESS, J
通讯作者：
WESS, J
DOI：
10.1523/jneurosci.0378-08.2008
发表时间：
2008-07-09
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Dittman JS;Kaplan JM
通讯作者：
Kaplan JM