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中国临床药理学与治疗学 ›› 2011, Vol. 16 ›› Issue (10): 1081-1085.

• 基础研究 •    下一篇

异丙酚在不同pH值环境下对苯甲酰苯甲酸ATP诱发的巨噬细胞嘌呤2X7受体电流的影响

刘红亮1, 戴体俊2   

  1. 1重庆市肿瘤研究所麻醉科,重庆 400030;
    2徐州医学院麻醉学系,徐州 221002,江苏
  • 收稿日期:2011-08-01 修回日期:2011-09-05 出版日期:2011-10-26 发布日期:2011-11-02
  • 通讯作者: 戴体俊,男,教授,硕士生导师,研究方向:全麻药的中枢作用机制。 E-mail: daitijun@163.com
  • 作者简介:刘红亮,男,医学博士,副教授,副主任医师,硕士生导师,研究方向:脑缺血损伤的发生机制。Tel: 13883686721, E-mail: liuhl75@163.com

Effect of propofol on BZATP induced P2X7-gated currents in RAW264.7 macrophages under different extracellular pH values

LIU Hong-liang1, DAI Ti-jun2   

  1. 1Department of Anesthesiology, Chongqing Cancer Hospital & Insititute, Chongqing 400030, China;
    2Department of Anesthesiology, Xuzhou Medical College, Xuzhou 221002, Jiangsu, China
  • Received:2011-08-01 Revised:2011-09-05 Online:2011-10-26 Published:2011-11-02

摘要: 目的: 观察在不同pH值条件下巨噬细胞膜嘌呤2X7(P2X7)受体电流对其特异性激动剂苯甲酰苯甲酸ATP (BZATP)的敏感性及异丙酚对P2X7受体电流的影响。方法: 应用培养的RAW264.7巨噬细胞,采用全细胞膜片钳技术,向细胞施加BZATP (10~10000 μmol/L) 5 s,记录电流,计算细胞外液pH值为 7.4 或 6.0 时BZATP的半效浓度(EC50)。观察异丙酚对P2X7受体电流的影响时,在细胞外液pH值为 6.5 或 7.4 时,向细胞预先施加异丙酚(1、3、10、30、100 μmol/L)1 min,再施加2倍EC50水平的BZATP持续5 s,计算异丙酚影响P2X7受体电流的半效抑制浓度(IC50)。观察异丙酚在不同pH值环境下对BZATP的浓度效应曲线的影响时,先施加IC50水平的异丙酚1 min,再施加不同浓度的BZATP并持续5 s,计算BZATP的EC50结果: BZATP在细胞外液pH值为 7.4 或 6.0 时诱发P2X7受体电流的EC50分别为(112±26) μmol/L 或(643±87) μmol/L。细胞外液pH值为 7.4 时,异丙酚可浓度依赖性地抑制P2X7受体电流,其IC50为(31±6) μmol/L,且此水平异丙酚可使BZATP的浓度效应曲线右移。细胞外液pH值为 6.0 时,异丙酚可浓度依赖性地增强P2X7受体电流,其EC50为(38±6) μmol/L,此浓度异丙酚使BZATP的浓度效应曲线发生左移。结论: 细胞外液pH值降低使P2X7受体对BZATP的敏感性下降,临床相关浓度的异丙酚在细胞外液pH值为 7.4 时对P2X7受体电流表现为剂量依赖性的抑制作用,但pH值为 6.0 时则呈现增强作用。

关键词: 异丙酚, 嘌呤2X7受体, 巨噬细胞, 细胞外液酸碱度

Abstract: AIM: To investigate the sensitivity of P2X7 receptor to its specific agonist BZATP and the effect of propofol on P2X7-gated currents in RAW264.7 macrophages under different extracellular pH values. METHODS: RAW264.7 cells were cultured, and whole-cell patch clamp technique was used. BZATP (10-10000 μmol/L) was applied for 5 seconds, the currents were recorded, and the EC50 value of BZATP was achieved under the extracellular pH value of 7.4 or 6.0. Propofol (1-100 μmol/L) was applied to the cells for 1 min, then BZATP with two times EC50 value was applied, the IC50 or EC50 value of propofol was achieved under different extracellular pH values. To investigate the effect of propofol on the dose-response curve of BZATP under different extracellular pH values, propofol with IC50 value was applied, and BZATP (10-10000 μmol/L) was applied for 5 seconds, the EC50 value of BZATP was achieved. RESULTS: BZATP could induce the inward currents in a dose-dependent manner, and the EC50 value of BZATP was (112±26) μmol/L and (643±87) μmol/L at extracellular pH value of 7.4 or 6.0. Propofol could inhibit P2X7-gated currents at pH 7.4, and the IC50 value was (31±6) μmol/L; but propofol increased P2X7-gated currents at pH 6.0, and the EC50 value was (38±6) μmol/L. The IC50 value of propofol made the dose-response curve of BZATP shifted rightward at pH 7.4, or leftward at pH 6.0. CONCLUSION: The sensitivity of P2X7 receptor to BZATP decreases when extracellular pH value changes from 7.4 to 6.0. Propofol with clinically related concentrations could inhibit P2X7-gated currents at pH 7.4, and increase P2X7-gated currents at pH 6.0 extracellularly.

Key words: Propofol, P2X7 receptor, Macrophage, Extracellular pH value

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