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

平滑肌细胞内Ca^2变化和受体介导的收缩调节的分子药理学

基本信息

批准号：
11672191
负责人：
SATOH Mitsutoshi
金额：
$ 2.3万
依托单位：
TOHO University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

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.

本研究对细胞内Ca~(2+)变化及受体介导的血管收缩调节进行了药理学研究。在豚鼠回肠纵行肌中。利用增强型CCD相机，用钙离子敏感的荧光探针Fluo-3，以33毫秒的间隔获得了钙离子振荡的二维图像。尼卡地平(10^&lt；-7&gt；M)显著降低钙离子振荡的最大荧光强度，抑制振荡频率，并有降低基础荧光强度的趋势。然而，河豚毒素(3×10~(-7)&gt；M)不影响这些振荡。佛波醇12，13-二丁酸酯(10^&lt；-7&gt；M)显著增加了最大荧光强度水平和钙离子振荡频率，并使其转变为稳定的和计时的钙振荡。环匹偶氮酸(3×10~(-5)&gt；M)也显著增加Ca~(2+)~(2+)和~(gt；)振荡频率。乙酰胆碱(10^&lt；-8&gt；M)使基础荧光强度、最大荧光强度和钙振荡频率增加，并加速其振荡。经环匹亚硝酸处理后，基础水平的荧光强度的增加被减弱。上述结果提示，豚鼠回肠平滑肌钙振荡的增强主要是由于受蛋白激酶C调控的L型钙通道的激活所致，而细胞内钙通道的排空可能是通过增加豚鼠回肠平滑肌钙内流来激活钙振荡的。