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Simultaneous assay of Calcium antagonistic and other antispsmodic activities of smooth muscle relaxants by "Ca reversal" phenomenon.

通过“Ca逆转”现象同时测定平滑肌松弛剂的钙拮抗和其他抗痉挛活性。

基本信息

批准号：
60571062
负责人：
UCHIDA Masaatsu
金额：
$ 1.09万
依托单位：
Meiji College of Pharmacy
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1986
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60571062/
关键词：
Calcium antagonist antispasmodics Calcium ion Calcium reversal inhibition Uterus smooth muscle オキシトシン

项目摘要

Ca ion, which is well known as a trigger of physiological responses may also act as an inhibitor of responses in lower concentrations than those act as triggers in rat uterine smooth muscle. Addition of resting level of Ca ion ( <10^(-8)> - <10^(-7)> M) reversed the contraction by oxytocin of uterine smooth muscle in Ca free solution after preincubation with 3mM EGTA for 1hr. This relaxation by Ca ion was named "Calcium reversal". This finding suggests that Ca ion at low concentrations has an inhibitory action. Ca reversal is manifested in the presence of Ca antagonists. So we tested availability of this phenomenon for the assay of Ca antagonistic activity. It was found that the system is very simple as the judgement is all or none and it is very useful because other antispasmodic actions can be determined simultaneously. <ED_(50)> values for Ca reversal of various drugs show their Ca antagonistic activity. The ratios of <ED_(50)> values for <10^(-4)> M Ca ion and for 3x <10^(-4)> M Ca ions represent selectivity of a drug for Ca channels. Further, the ratio in high <K^+> solution clearly shows the selectivity of a Ca antagonist for voltage-operated Ca channels. Thus this system is very useful for the assay of Ca antagonistic activities, which are very important for drug therapy.

众所周知，钙离子作为生理反应的触发物，在较低浓度下也可能作为反应的抑制剂，而在大鼠子宫平滑肌中作为触发物。加入静息水平的Ca离子(<10^（-8)> - <10^(-7)> M）可逆转无Ca溶液中3mM EGTA预孵育1hr后子宫平滑肌的催产素收缩。这种钙离子的弛豫被命名为“钙逆转”。这表明低浓度的钙离子具有抑制作用。钙逆转表现在钙拮抗剂的存在下。因此，我们测试了这种现象在钙拮抗活性测定中的有效性。结果表明，该系统的判断是全或无，非常简单，而且可以同时确定其他抗痉挛动作，因此非常有用。各种药物钙逆转的<ED_(50)>值显示其钙拮抗活性。<10^(-4)> M Ca离子<ED_(50)>值和< 3 ^(-4)> M Ca离子<ED_(50)>值的比值表示药物对Ca通道的选择性。此外，在高<K^+>溶液中的比率清楚地表明钙拮抗剂对电压操作的钙通道的选择性。因此，该系统可用于钙拮抗活性的测定，对药物治疗具有重要意义。