期刊
PHARMACOLOGY & THERAPEUTICS
卷 180, 期 -, 页码 144-160出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2017.07.001
关键词
Connexin; Pannexin; Hemichannel; Gap junction; Inhibitor
资金
- European Research Council (ERC) [335476]
- Fund for Scientific Research Flanders (FWO) [G009514N, G010214N]
- University Hospital of the Vrije Universiteit Brussel-Belgium (Willy Gepts Fonds UZ-VUB)
While gap junctions support the exchange of a number of molecules between neighboring cells, connexin hemichannels provide communication between the cytosol and the extracellular environment of an individual cell. The latter equally holds true for channels composed of pannexin proteins, which display an architecture reminiscent of connexin hemichannels. In physiological conditions, gap junctions are usually open, while connexin hemichannels and, to a lesser extent, pannexin channels are typically closed, yet they can be activated by a number of pathological triggers. Several agents are available to inhibit channels built up by connexin and pannexin proteins, including alcoholic substances, glycyrrhetinic acid, anesthetics and fatty acids. These compounds not always strictly distinguish between gap junctions, connexin hemichannels and pannexin channels, and may have effects on other targets as well. An exception lies with mimetic peptides, which reproduce specific amino acid sequences in connexin or pannexin primary protein structure. In this paper, a state-of-the-art overview is provided on inhibitors of cellular channels consisting of connexin and pannexins with specific focus on their mode-of-action and therapeutic potential. (C) 2017 Elsevier Inc. All rights reserved.
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