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首页> 外文期刊>Journal of Cellular Physiology >Regulation and Functional Implications of Opioid Receptor Splicing in Opioid Pharmacology and HIV Pathogenesis
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Regulation and Functional Implications of Opioid Receptor Splicing in Opioid Pharmacology and HIV Pathogenesis

机译：阿片类药物监管和功能的影响拼接在阿片受体药理学和艾滋病毒发病机理

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Despite the identification and characterization of four opioid receptor subtypes and the genes from which they are encoded, pharmacological data does not conform to the predications of a four opioid receptor model. Instead, current studies of opioid pharmacology suggest the existence of additional receptor subtypes; however, no additional opioid receptor subtype has been identified to date. It is now understood that this discrepancy is due to the generation of multiple isoforms of opioid receptor subtypes. While several mechanisms are utilized to generate these isoforms, the primary mechanism involves alternative splicing of the pre-mRNA transcript. Extensive alternative splicing patterns for opioid receptors have since been identified and discrepancies in opioid pharmacology are now partially attributed to variable expression of these isoforms. Recent studies have been successful in characterizing the localization of these isoforms as well as their specificity in ligand binding; however, the regulation of opioid receptor splicing specificity is poorly characterized. Furthermore, the functional significance of individual receptor isoforms and the extent to which opioid- and/or HIV-mediated changes in the opioid receptor isoform profile contributes to altered opioid pharmacology or the well-known physiological role of opioids in the exacerbation of HIV neurocognitive dysfunction is unknown. As such, the current review details constitutive splicing mechanisms as well as the specific architecture of opioid receptor genes, transcripts, and receptors in order to highlight the current understanding of opioid receptor isoforms, potential mechanisms of their regulation and signaling, and their functional significance in both opioid pharmacology and HIV-associated neuropathology. J. Cell. Physiol. 231: 976-985, 2016. (c) 2015 Wiley Periodicals, Inc.
机译：尽管识别和描述四个阿片受体亚型的基因它们编码、药理数据呢不符合四类鸦片的论断受体模型。阿片类药物药理学建议的存在额外的受体亚型;额外的阿片受体亚型确定日期。这种差异是由于生成的多种亚型的阿片受体亚型。同时利用几种机制来生成这些亚型,涉及的主要机制可变剪接的pre-mRNA成绩单。广泛的可变剪接模式阿片受体已经被确认现在在阿片类药物药理学差异部分归因于变量表达式这些亚型。成功的本地化特征这些亚型以及他们的特异性配体结合;剪接受体特异性差为特征。个别受体亚型的重要性阿片类药物的程度,和/或HIV-mediated阿片受体同种型剖面的变化对阿片类药物药理学或改变著名的阿片类药物的生理作用神经认知功能障碍是艾滋病的恶化未知的。以及本构剪接机制特定架构的阿片受体基因,成绩单,受体以突出当前对阿片受体的理解亚型,潜在的机制监管和信号,其功能阿片类药物药理学和意义艾滋病毒相关神经病理学。231: 976 - 985, 2016。公司。

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