四氢原小檗碱类药物对培养大鼠单个心肌细胞内游离Ca2+的影响

用Fura-2/AM技术和AR-CM-MIC阳离子测定系统,直接测定了四氢小檗碱(tetrahy-droberberine,THB)、左旋四氢巴马汀(l-tetrahydropalmatine,THP)和左旋千金藤立定(l-stepholidine,SPO)对培养大鼠单个心室肌细胞内游离钙(Ca²⁺]i)的影响,并与维拉帕米(Ver)做了比较。结果显示,THB,THP,SPD浓度为10～100μmol·L^-1时,均可使静息Ca²⁺]i轻度升高,河豚毒素不能抑制之;浓度为1～100μmol·L^-1时,可明显抑制高K+引起的Ca²⁺]i增高;30μmol·L^-1对胞外高Ca²⁺和去甲肾上腺素引起的Ca²⁺]i增高也有明显的抑制作用,但均较Ver的抑制作用为弱;THPB对哇巴因引起的ca²⁺]i升高无明显抑制作用。结果提示,THB,THP,SPD在抑制电压依赖性钙通道从而影响细胞膜ca²⁺]i内流方面与Ver相似,但比Ver弱。

EFFECTS OF TETRAHYDROPROTOBERBERINES ON CYTOSOLIC FREE CALCIUM IN CULTURED RAT SINGLE MYOCARDIAL CELLS

Effect of tetrahydroberberine(THB),l-tetrahydropalmatine(THP) and l-stepholi-dine(SPD) were supposed to be related to the blocking of calcium influx. In this paper,using Fura-2/AM and AR- CM-MIC cation measurement system,the effects of THB,THP and SPD on cytosolicfree calcium(Ca²⁺]i) in cultured rat single myocardial cells were examined and compared withverapamil(Ver). TH,THP and SPD(10～100μmol·L^-1) were found to increase restingCa²⁺]i gently,which was not depressed by tetrodotoxin. THB,THP and SPD(1～100μmol·L^-1)were also shown to inhibit the KCl- inducedCa2+]i elevation, the IC50 values of THBand SPD were 50.9(95%confidence limits: 18.5～140)μmol·L^-1 and 23.5(95%confidencelimits 7.6～73.4)μmol·L^-1, respectively. THB, THP and SPD 30μmol·L^-1 were also shown toinhibit the elevation ofCa²⁺]i induced by high extracellular calcium and norepinephrine; but theinhibitory effects of these drugs were weaker than those of Ver. The three compounds showed nosignificant effect on ouabain inducedCa²⁺]i increas1e. These results suggest that the inhibitory effects of THB, THP and SPD on Ca²⁺]i in myocite by blocking voltage- dependent calcium channels were similar but inferior to Ver.