PT - JOURNAL ARTICLE AU - Weihong Ma AU - Hui Hui AU - Pablo Pelegrin AU - Annmarie Surprenant TI - Pharmacological Characterization of Pannexin-1 Currents Expressed in Mammalian Cells AID - 10.1124/jpet.108.146365 DP - 2009 Feb 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 409--418 VI - 328 IP - 2 4099 - http://jpet.aspetjournals.org/content/328/2/409.short 4100 - http://jpet.aspetjournals.org/content/328/2/409.full SO - J Pharmacol Exp Ther2009 Feb 01; 328 AB - 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) ≈ disodium 4-acetamido-4′-isothiocyanato-stilben-2,2′-disulfonate ≈ 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 P2X7 receptor (P2X7R), DIDS was found to act as a P2X7R antagonist to inhibit ATP-evoked currents, but none of the other compounds inhibited P2X7R 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 P2X7R activation. The American Society for Pharmacology and Experimental Therapeutics