| Pharmacological characterization of pannexin-1 currents expressed in mammalian cells. | |
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MedLine Citation:
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PMID: 19023039 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pannexin (Panx) 1 is a widely expressed protein that shares structural, but not amino acid, homology with gap junction proteins, the connexins. Panx1 does not form gap junctions in mammalian cells, but it may function as a plasma membrane hemichannel. Little is known of the pharmacological properties of panx1 expression in mammalian cells. Here, we identify three variants in the human PANX1 gene. We expressed these variants and mouse Panx1 in mammalian cells and compared Panx1-induced currents. All human Panx1 variants and the mouse Panx1 showed identical protein expression levels, localization patterns, and functional properties, although the frequency of functional expression was species-dependent. Panx1 currents were independent of changes in extracellular or intracellular calcium or phospholipase C transduction. We found compounds that inhibited Panx1 currents with a rank order of potency: carbenoxolone > disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS) approximately disodium 4-acetamido-4'-isothiocyanato-stilben-2,2'-disulfonate approximately 5-nitro-2-(3-phenylpropylamino)benzoic acid > indanyloxyacetic acid 94 >> probenecid >> flufenamic acid = niflumic acid. Triphosphate nucleotides (ATP, GTP, and UTP) rapidly and reversibly inhibited Panx1 currents via mechanism(s) independent of purine receptors. When Panx1 was coexpressed with purinergic P2X(7) receptor (P2X(7)R), DIDS was found to act as a P2X(7)R antagonist to inhibit ATP-evoked currents, but none of the other compounds inhibited P2X(7)R currents. This is the first detailed pharmacological characterization of Panx1-mediated currents in mammalian cells and sheds new, although contradictory, light on the hypothesis that Panx1 acts as a hemichannel to allow passage of large molecules in response to P2X(7)R activation. |
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Authors:
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Weihong Ma; Hui Hui; Pablo Pelegrin; Annmarie Surprenant |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-11-20 |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 328 ISSN: 1521-0103 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-01-23 Completed Date: 2009-02-23 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: United States |
Other Details:
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Languages: eng Pagination: 409-18 Citation Subset: IM |
Affiliation:
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Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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pharmacology Animals Biochemical Processes / drug effects, physiology* Calcium / metabolism Cell Membrane Permeability / drug effects, physiology* Chloride Channels / antagonists & inhibitors, metabolism Connexins / drug effects, genetics, physiology* Humans Membrane Potentials / drug effects, physiology* Mice Nerve Tissue Proteins / drug effects, genetics, physiology* Organic Anion Transporters / antagonists & inhibitors Polymorphism, Single Nucleotide / drug effects, genetics* RNA Splicing / drug effects, genetics* Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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//Biotechnology and Biological Sciences Research Council |
| Chemical | |
Reg. No./Substance:
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0/Chloride Channels; 0/Connexins; 0/Nerve Tissue Proteins; 0/Organic Anion Transporters; 0/PANX1 protein, human; 56-65-5/Adenosine Triphosphate; 7440-70-2/Calcium |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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