羟苯氨酮对心肌肌钙蛋白C与Ca^(2+)亲和力的影响

EFFECT OF OXYPHENAMONE ON CA 2+ AFFNITY OF CARDIAC TROPONIN C

目的：探讨羟苯氨酮（ｏｘｙｐｈｅｎａｍ ｏｎｅ ， Ｏｘｙ） 的钙增敏机理。方法：从牛心肌组织中提取ｃ Ｔｎ Ｃ，采用荧光探针标记法观察 Ｏｘｙ 对ｃ Ｔｎ Ｃ 与 Ｃａ２ ＋ 亲和力的影响，并和已知的钙增敏剂 Ｍ Ｃ Ｉ１５４ 、磺甲唑（ｓｕｌｍａｚｏｌｅ ， Ｓｕｌ） 作比较。结果： Ｏｘｙ 显著增加ｃ Ｔｎ Ｃ 和 Ｃａ２ ＋ 的亲和力，且呈剂量与效应相关。而５０ μｍ ｏｌ· Ｌ－ １ Ｍ Ｃ Ｉ１５４ 或 Ｓｕｌ 对ｃ Ｔｎ Ｃ 和 Ｃａ２ ＋ 亲和力曲线均无显著影响。结论： Ｏｘｙ 的钙增敏机理可能与直接增加ｃ Ｔｎ Ｃ 与 Ｃａ２ ＋ 的亲和力有关。

AIM: To explore the molecular mechanism of the calcium sensitizing effect of oxyphenamone(Oxy). METHODS: Cardiac troponin C(cTn C) was purified from cattle cardiac muscle and labeled with fluorescent probe, dansyl chloride. The effect of Oxy on the affinity of cTn C to Ca 2+ was studied and compared with those of MCI 154 and sulmazole(Sul). RESULTS: Oxy was shown to improve the affinity of Ca 2+ dose dependently. Oxy 10 μmol·L -1 slightly shifted the cTn C—Ca 2+ affinity curve to the left, but showed no significance while Oxy 25 μmol·L -1 significantly shifted the curve to the left. Oxy 50 μmol·L -1 showed more potent action, shifting the affinity curve to the left by 0 2 pCa unit. In contrast, MCI 154 or Sul 50 μmol·L -1 showed no significant influence on the affinity curve. CONCLUSION: These results suggest that the positive inotropic action of Oxy on cardiac muscle is, at least, partially mediated by increasing the sensitivity of cTn C to Ca 2+ , the calcium sensitizing effect of MCI 154 and Sul may be mediated otherwise besides directly increasing the affinity of cTn C to Ca 2+ .