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首页> 外文期刊>Pharmacogenetics and genomics >Functional consequences of nonsynonymous single nucleotide polymorphisms in the CB2 cannabinoid receptor.
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Functional consequences of nonsynonymous single nucleotide polymorphisms in the CB2 cannabinoid receptor.

机译：CB2大麻受体中非同义单核苷酸多态性的功能后果。

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摘要

OBJECTIVE: To test the hypothesis that the two nonsynonymous single nucleotide polymorphisms at the CB2 cannabinoid receptor gene may have functional consequences on human CB2. METHODS: Q63R, H316Y, and Q63R/H316 mutations were made in recombinant human CB2 by the method of site-directed mutagenesis. After these mutant CB2 receptors were stably transfected into HEK293 cells, ligand binding, ligand-induced activity, and constitutive activity assays were performed to test the functional significance of these mutations. RESULTS: In general, our results showed that the CB2 polymorphic receptors are able to bind cannabinoid ligands and mediate signal transduction. However, in ligand-induced cyclic AMP accumulation assays, the cannabinoid agonists WIN55212-2 and 2-arachidonoylglycerol had reduced efficacy in cells expressing the polymorphic receptors as compared with the CB2 wild-type receptor. Furthermore, in constitutive activity assays, the H316Y and Q63R/H316Y polymorphic receptors exhibited higher constitutive activity than the CB2 wild-type receptor. CONCLUSION: Our data shows that the presence of the polymorphisms at both positions 63 and 316 produce alterations in the CB2 receptor functions. Moreover, these findings strengthen the idea that the CB2 polymorphic receptors may contribute to the etiology of certain diseases.
机译：目的：验证以下假设：CB2大麻素受体基因的两个非同义单核苷酸多态性可能对人CB2具有功能性影响。方法：采用定点诱变方法在重组人CB2中产生Q63R，H316Y和Q63R / H316突变。将这些突变的CB2受体稳定转染入HEK293细胞后，进行配体结合，配体诱导的活性和组成性活性测定，以测试这些突变的功能意义。结果：总的来说，我们的结果表明CB2多态性受体能够结合大麻素配体并介导信号转导。但是，在配体诱导的环AMP积累测定中，与CB2野生型受体相比，大麻素激动剂WIN55212-2和2-花生四烯酰基甘油在表达多态性受体的细胞中的功效降低。此外，在组成性活性测定中，H316Y和Q63R / H316Y多态性受体表现出比CB2野生型受体更高的组成性活性。结论：我们的数据表明，在位置63和316处均存在多态性，从而导致CB2受体功能发生改变。而且，这些发现加强了CB2多态性受体可能有助于某些疾病的病因的想法。

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