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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Peripheral benzodiazepine receptors and mitochondrial function.
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Peripheral benzodiazepine receptors and mitochondrial function.

机译：外周苯并二氮杂receptor受体和线粒体功能。

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摘要

For over 20 years, numerous investigations have focused on elucidating the function of the peripheral benzodiazepine receptor (PBR). This relatively small protein (18kDa) arouses great interest because of its association with numerous biological functions, including the regulation of cellular proliferation, immunomodulation, porphyrin transport and heme biosynthesis, anion transport, regulation of steroidogenesis and apoptosis. Although the receptor was first identified as a binding site for the benzodiazepine, diazepam, in peripheral organ systems, the PBR was subsequently found to be distinct from the central benzodiazepine receptor (CBR) in terms of its pharmacological profile, structure, subcellular localization, tissue distribution and physiological functions. The PBR is widely expressed throughout the body, with high densities found in steroid-producing tissues. In contrast, its expression in the CNS is restricted to ependymal cells and glia. The benzodiazepine Ro5-4864 and the isoquinoline carboxamide PK11195 exhibit nanomolar affinity for the PBR, and are the archtypic pharmacological tools for characterizing the receptor and its function. Primary among these functions are its regulation of steroidogenesis and apoptosis, which reflect its mitochondrial localization and involvement in oxidative processes. This review will evaluate the basic pharmacology and molecular biology of the PBR, and highlight its role in regulating mitochondrial function, the mitochondrial transmembrane potential and its sensitivity to reactive oxygen species (ROS), and neurosteroid synthesis, processes relevant to the pathogenesis of a number of neurological and neuropsychiatric disorders.
机译：20多年来，许多研究集中于阐明外周苯二氮卓类受体（PBR）的功能。这种相对较小的蛋白质（18kDa）由于具有许多生物学功能，包括调节细胞增殖，免疫调节，卟啉转运和血红素生物合成，阴离子转运，调节类固醇生成和凋亡而引起了极大的兴趣。尽管该受体最初被确定为苯并二氮杂地西epa在外周器官系统中的结合位点，但随后发现在其药理学特征，结构，亚细胞定位，组织方面，PBR与中枢苯并二氮杂receptor受体（CBR）不同。分布和生理功能。 PBR在全身广泛表达，在产生类固醇的组织中发现高密度。相反，其在中枢神经系统中的表达仅限于室管膜细胞和神经胶质细胞。苯二氮卓Ro5-4864和异喹啉羧酰胺PK11195对PBR表现出纳摩尔亲和力，是表征受体及其功能的原型药理学工具。这些功能中的主要功能是其对类固醇生成和细胞凋亡的调节，这反映了其线粒体的定位和参与氧化过程。这篇综述将评估PBR的基本药理学和分子生物学，并着重介绍其在调节线粒体功能，线粒体跨膜电位及其对活性氧（ROS）和神经甾体合成的敏感性等方面的作用，这些过程与许多发病机制相关神经系统疾病和神经精神疾病。

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