Molecular pharmacology of intracellular Ca^<2+> changes and receptor-mediated regulation of contraction in smooth muscle

在这项研究中，研究了细胞内Ca^2+变化和受体介导的平滑肌收缩调节的药理学特征。豚鼠回肠纵行平滑肌。用Ca^2+敏感的荧光探针fluo-3，使用增强型CCD照相机，以33毫秒的间隔获得Ca^2+振荡的二维图像。尼卡地平（10 μ <-7>M）显著降低了Ca^2+振荡的最大荧光强度水平，抑制了振荡频率，并有降低荧光强度基础水平的趋势。然而，河豚毒素（3 × 104 μ <-7>M）不影响这些振荡。10 μ M佛波醇12，13-二丁酸酯<-7>显著增加荧光强度的最大值和Ca^2+振荡的频率，并使它们变为稳定的计时Ca^2+振荡。环匹阿尼酸（3 × 10^<-5>M）也显著增加了Ca^2+振荡的频率。乙酰胆碱（10 μ <-8>M）可增加荧光强度的基础值和最大值以及Ca^2+振荡的频率，并加速它们的启动。然后通过环匹阿尼酸处理降低荧光强度的基础水平的增加。上述结果提示，豚鼠回肠平滑肌Ca^2+振荡的增强主要是由于蛋白激酶C调节的L型Ca^2+通道的激活，细胞内Ca^2+库的排空可能通过Ca^2+内流的增加而激活Ca^2+振荡。

In this study pharmacological profiles of intracellular Ca^<2+> changes and receptor-mediated regulation of contraction in smooth muscle were studied. In ileal longitudinal smooth muscle from guinea pig. Two-dimensional images of Ca^<2+> oscillations were obtained at 33-msec intervals with a Ca^<2+>-sensitive fluorescence probe, fluo-3 using the intensified CCD camera. Nicardipine (10^<-7> M) significantly decreased the maximum level of fluorescence intensity of the Ca^<2+> oscillations, inhibited the frequency of the oscillations, and tended to decrease the basal level of fluorescence intensity. However, tetrodotoxin (3 X 10^<-7> M) did not affect these oscillations. Phorbol 12, 13-dibutyrate (10^<-7> M) significantly increased the maximum level of fluorescence intensity and the frequency of Ca^<2+> oscillations, and changed them to steady and chronometric Ca^<2+> oscillations. Cyclopiazonic acid (3 X 10^<-5> M) also significantly increased the frequency of Ca^<2+> oscillations. Acetylcholine (10^<-8> M) increased the basal and maximum level of fluorescence intensity and the frequency of Ca^<2+> oscillations, and accelerated their on set. The increase of basal level of fluorescence intensity was then decreased by cyclopiazonic acid treatment. These results suggest that the augmentation of Ca^<2+> oscillations is mainly due to the activation of L-type Ca^<2+> channels, which is modulated by protein kinase C, and that the emptying of intracellular Ca^<2+> stores may activate the Ca^<2+> oscillations mediated through the increase of Ca^<2+> influx in ileal smooth muscle of guinea pig.