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  • Title: Inhibitors of nonselective cation channels in cells of the blood-brain barrier.
    Author: Popp R, Englert HC, Lang HJ, Gögelein H.
    Journal: EXS; 1993; 66():213-8. PubMed ID: 7505652.
    Abstract:
    In the antiluminal membrane of isolated capillaries of rat and porcine brain (blood-brain barrier) nonselective cation channels with g = 31 pS were observed in cell-excised membrane patches. The channel inactivated by decreasing cytosolic Ca2+ below 1 microM and was inhibited by 1 mM ATP on the intracellular side. Anions and divalent cations did not pass the channel, but Na+ and K+ were equally permeant. Like the nonselective cation channel of rat exocrine pancreatic cells, the channel in cerebral capillary endothelial cells was inhibited reversibly by derivatives of diphenylamine-2-carboxylate (DPC), like 3',5-dichlorodiphenylamine-2-carboxylic acid (DCDPC, ki = 1 microM), and flufenamic acid (ki = 4.9 microM). 4'-methyldiphenylamine-2-carboxylic acid (4-MDPC), 5-chloro-2(3-trifluormethylphenylamino)-3-nitrobenzoic acid, and 5-nitro-2-(3-phenylpropylamino)-2-carboxylic acid (NPPB), as well as the antiinflammatory drug ((Z)-5-chloro2,3-dihydro-3-(hydroxy-2-thienylmethylene)-2-ox o-1H-indole-1- carboxamide (Tenidap)) had a relatively low blocking potency (ki > 10 microM). Gadolinium (10 microM), a blocker of stretch-activated channels, inhibited the nonselective cation channel potently.
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