Histamine-mediated increases in cytosolic [Ca2+] involve different mechanisms in human pulmonary artery smooth muscle and endothelial cells.
Histamine-mediated increases in cytosolic [Ca2+] involve different mechanisms in human pulmonary artery smooth muscle and endothelial cells.
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发表时间：
2006
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通讯作者：
J. Mauban;K. Wilkinson;C. Schach;J. Yuan
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作者：
J. Mauban;K. Wilkinson;C. Schach;J. Yuan
用组胺激动剂刺激人肺动脉平滑肌细胞 (PASMC) 和内皮细胞 (PAEC) 显示出相似的 Ca(2+) 释放时空模式。在不存在细胞外Ca(2+) 的情况下，观察到胞质Ca(2+) 浓度([Ca(2+)](cyt)) 变化的持续升高和振荡模式。通过用 10 µM 环吡嗪酸 (CPA；15-30 分钟) 被动消耗细胞内 Ca (2+) 储备，在 PASMC 和 PAEC 中诱导电容性 Ca(2+) 进入 (CCE)。吡唑衍生物BTP2抑制CPA激活的Ca(2+)内流，表明CPA敏感的内部储备的消耗足以诱导PASMC和PAEC中的CCE。在细胞暴露于CPA、毒胡萝卜素、咖啡因、兰尼碱、FCCP或巴弗洛霉素后，检查组胺介导的Ca(2+)释放的来源。在浸泡在无 Ca(2+) 溶液中的 PASMC 中，CPA 处理几乎消除了组胺诱导的 [Ca(2+)](cyt) 升高。然而，在浸入无 Ca(2+) 溶液的 PAEC 中，CPA 处理消除了组胺诱导的 [Ca(2+)](cyt) 持续振荡上升，但不影响 [Ca(2+)](cyt) 的初始短暂增加。此外，用CPA（或毒胡萝卜素）和咖啡因（和兰尼定）、FCCP或巴弗洛霉素组合治疗PAEC并不能消除组胺诱导的短暂[Ca(2+)](细胞色素)增加。这些观察结果表明 1) CPA 敏感储备的耗尽足以导致 PASMC 和 PAEC 中的 CCE； 2) PAEC 中 CCE 的诱导不需要耗尽所有内部 Ca(2+) 储备； 3）PASMC中可释放组胺的内部储存主要是CPA敏感储存； 4) PAEC除了CPA敏感的功能池外，还包含对CPA不敏感的其他存储，毒胡萝卜素，咖啡因，兰尼定，FCCP和巴弗洛霉素； 5) 尽管 PAEC 中的 CPA 不敏感储存可能不会导致 CCE，但它们有助于组胺介导的 Ca(2+) 释放。
Agonist stimulation of human pulmonary artery smooth muscle cells (PASMC) and endothelial cells (PAEC) with histamine showed similar spatiotemporal patterns of Ca(2+) release. Both sustained elevation and oscillatory patterns of changes in cytosolic Ca(2+) concentration ([Ca(2+)](cyt)) were observed in the absence of extracellular Ca(2+). Capacitative Ca(2+) entry (CCE) was induced in PASMC and PAEC by passive depletion of intracellular Ca(2+) stores with 10 microM cyclopiazonic acid (CPA; 15-30 min). The pyrazole derivative BTP2 inhibited CPA-activated Ca(2+) influx, suggesting that depletion of CPA-sensitive internal stores is sufficient to induce CCE in both PASMC and PAEC. The recourse of histamine-mediated Ca(2+) release was examined after exposure of cells to CPA, thapsigargin, caffeine, ryanodine, FCCP, or bafilomycin. In PASMC bathed in Ca(2+)-free solution, treatment with CPA almost abolished histamine-induced rises in [Ca(2+)](cyt). In PAEC bathed in Ca(2+)-free solution, however, treatment with CPA eliminated histamine-induced sustained and oscillatory rises in [Ca(2+)](cyt) but did not affect initial transient increase in [Ca(2+)](cyt). Furthermore, treatment of PAEC with a combination of CPA (or thapsigargin) and caffeine (and ryanodine), FCCP, or bafilomycin did not abolish histamine-induced transient [Ca(2+)](cyt) increases. These observations indicate that 1) depletion of CPA-sensitive stores is sufficient to cause CCE in both PASMC and PAEC; 2) induction of CCE in PAEC does not require depletion of all internal Ca(2+) stores; 3) the histamine-releasable internal stores in PASMC are mainly CPA-sensitive stores; 4) PAEC, in addition to a CPA-sensitive functional pool, contain other stores insensitive to CPA, thapsigargin, caffeine, ryanodine, FCCP, and bafilomycin; and 5) although the CPA-insensitive stores in PAEC may not contribute to CCE, they contribute to histamine-mediated Ca(2+) release.