半胱氨酸-白三烯D4诱导胞浆Ca2+升高和人逼尿肌收缩。

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布什鲁什K，安徒生L，诺德林J，霍恩T，布什鲁什P

半胱氨酸-白三烯D4诱导胞浆Ca2+升高和人逼尿肌收缩。

《泌尿学杂志》2003年8月;170(2 Pt 1):638-44。

PubMed ID

12853847 (PubMed视图

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摘要

目的:细胞内Ca2+在人逼尿肌平滑肌细胞(SMCs)激活中的作用是关键的。最近，我们发现肥大细胞来源的促炎介质白三烯D(4) (LTD(4))诱导人逼尿肌细胞内游离Ca2+ ([Ca2+](i))的增加。在目前的研究中，我们研究了LTD(4)诱导[Ca2+](i)增加的机制，并通过测量人逼尿肌组织的力量发展来测试LTD(4)是否诱导肌肉收缩。材料和方法:从接受膀胱镜检查的良性膀胱疾病患者中获得人逼尿肌smc培养。利用微荧光光谱法和动态视频成像技术在fura-2负载的SMCs中测量[Ca2+](i)。用特制的微型肌描记仪监测收缩力。结果:观察到[Ca2+](i)和力的自发振荡。在缺乏钙的情况下，这些振荡就不存在了。LTD(4)引起[Ca2+](i)和等距力的浓度依赖性增加。钙只从细胞内储存物中释放出来。 Increases in [Ca2+](i) and force were inhibited in dose dependent fashion by the LTD(4) receptor antagonists montelukast and zafirlukast. Likewise, LTC(4) and LTE(4) induced an increase in [Ca2+](i) and contractile force in the rank order LTD(4) >LTC(4) >LTE(4). Inhibition of Ca2+ induced Ca2+ release (CICR) with thapsigargin and ryanodine suggested the presence of a functional CICR in SMCs. CONCLUSIONS: To our knowledge this study demonstrates for the first time that the cysteinyl-leukotriene LTD(4) induces contraction in human detrusor SMCs. LTD(4) induced force and increased [Ca2+](i) were entirely dependent on Ca2+ release from intracellular stores. The action of LTD(4) on force development and increased [Ca2+](i) appeared to be specific, mediated by the binding and activation of specific LTD(4) receptors on SMCs. Also, to our knowledge this report is the first to show that human detrusor SMCs are sensitive to ryanodine, consistent with the hypothesis that a CICR is present and functional in these cells. The presence and role of endogenous cysteinyl leukotrienes for normal contractile functioning of the human detrusor during inflammation remains to be elucidated.

引用本文的药物库数据

药物靶点

药物	目标	种类	生物	药理作用	行动
白三烯C4	半胱氨酸白三烯受体1	蛋白质	人类	未知的	不可用	细节
白三烯D4	半胱氨酸白三烯受体1	蛋白质	人类	未知的	不可用	细节