Pharmacological differentiation of the P2X₇ receptor and the maitotoxin-activated cationic channel

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• 作者：Lundy ; Paul M. ; Nelson ; Peggy ; Mi ; Lei ; Frew ; Robert ; Minaker ; Sean ; Vair ; Cory ; Sawyer ; Thomas W.
• 关键词：ATP-P2X₇ receptor ; Maitotoxin ; Cytolytic pore ; Cell death ; Ca²⁺
• 刊名：European Journal of Pharmacology
• 出版年：2004
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：March 8, 2004
• 卷：487
• 期：1-3
• 页码：17-28
• 文件大小：501 K

摘要

The ATP-P2X₇ receptor subtype and a maitotoxin-activated ion channel were studied to determine factors which identify them as separate entities in the control of a cytotolytic pore. Activation of ATP-P2X₇ receptors with 2′-3′-O-(benzylbenzyl) ATP (BzATP) or maitotoxin ion channels resulted in influx of ethidium bromide and cell death. Maitotoxin (25–250 pM)-induced ethidium bromide uptake and cell death was sensitive to extracellular Ca²⁺, the ionic composition of the buffer, reduced by the calmodulin inhibitor W7, (N-(s-aminohexyl)-5-chloro-1-naphthalenesulfonamide), (10–100 μM) but unaffected by the ATP-P2X₇ receptor antagonist oxidized ATP, (adenosine 5′-triphosphate periodate oxidized sodium salt) (oATP). BzATP (10–200 μM)-induced ethidium bromide uptake and cell death were inhibited by oATP, unaffected by W7, inhibited by high ionic concentrations but only slightly dependant on external Ca²⁺. These results are consistent with the existence of a pharmacological mechanism for controlling cell death consisting of an ATP-P2X₇ receptor, a maitotoxin-activated ion channel and a cytolytic pore.