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Pannexin 通道的药理学。

Pharmacology of pannexin channels.

机构信息

Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.

Department of Molecular Physiology and Biophysics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.

出版信息

Curr Opin Pharmacol. 2023 Apr;69:102359. doi: 10.1016/j.coph.2023.102359. Epub 2023 Feb 28.

Abstract

Pannexin channels play fundamental roles in regulating inflammation and have been implicated in many diseases including hypertension, stroke, and neuropathic pain. Thus, the ability to pharmacologically block these channels is a vital component of several therapeutic approaches. Pharmacologic interrogation of model systems also provides a means to discover new roles for pannexins in cell physiology. Here, we review the state of the art for agents that can be used to block pannexin channels, with a focus on chemical pharmaceuticals and peptide mimetics that act on pannexin 1. Guidance on interpreting results obtained with pannexin pharmacologics in experimental systems is discussed, as well as strengths and caveats of different agents, including specificity and feasibility of clinical application.

摘要

缝隙连接通道在调节炎症中起着重要作用,并与包括高血压、中风和神经病理性疼痛在内的许多疾病有关。因此,能够用药理学方法阻断这些通道是几种治疗方法的重要组成部分。对模型系统的药理学研究也为缝隙连接蛋白在细胞生理学中的新作用提供了一种手段。在这里,我们回顾了可用于阻断缝隙连接通道的药物的最新进展,重点介绍了作用于缝隙连接蛋白 1 的化学药物和肽模拟物。讨论了在实验系统中使用缝隙连接蛋白药理学获得的结果的解释指南,以及不同药物的优缺点,包括特异性和临床应用的可行性。

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