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

钙离子，这是众所周知的生理反应的触发器，也可以作为反应的抑制剂，在较低的浓度比那些作为触发器在大鼠子宫平滑肌。加入静息水平的Ca ~（2+）（<10^（-8）> - <10^（-7）> M）可逆转缩宫素引起的子宫平滑肌收缩。钙离子的这种弛豫被称为“钙逆转”。这一发现表明，低浓度的Ca离子具有抑制作用。Ca拮抗剂的存在下表现出Ca逆转。因此，我们测试了这种现象的可用性的钙拮抗活性的测定。结果发现，该系统是非常简单的判断是全部或没有，它是非常有用的，因为它可以同时确定其他解痉作用。各种药物钙拮抗作用的<艾德_（50）>值显示其钙拮抗活性。<10^（-4）> M Ca离子和3 x <10^（-4）> M Ca离子的<艾德_（50）>值的比值代表药物对Ca通道的选择性。此外，高K^+溶液中的比值清楚地表明了钙拮抗剂对电压操纵性钙通道的选择性。因此，该系统是非常有用的钙拮抗活性的测定，这是非常重要的药物治疗。

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.