Endothelin-1 Induces Contraction via a Syk-Mediated p38 Mitogen-Activated Protein Kinase Pathway in Rat Aortic Smooth Muscle

Journal of Pharmacological Sciences

Bokyung Kim²  Hwan Myung Lee²  Junghwan Kim¹  Hui Yul Roh²  Hyo-Jun Park²  So Hee Lee²  Chang-Kwon Lee²  Kyung-Jong Won²  Hyo Jin Kim² 

[1] Department of Physical Therapy, College of Natural Science, Yongin University, Korea;Departments of Physiology, College of Medicine, Konkuk University, Korea

关键词: contraction;    spleen tyrosine kinase (Syk);    rat aortic smooth muscle cell (RASMC);    endothelin-1;    p38 mitogen-activated protein kinase (MAPK);   

DOI  :  10.1254/jphs.FP0070039

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(37)Cited-By(14)Although spleen tyrosine kinase (Syk) has crucial roles in various cells, its function on vascular smooth muscle contraction has not been determined. In the present study, we performed experiments to determine if Syk contributes to the endothelin-1 (ET-1)-mediated contraction in rat aortic smooth muscle. ET-1-induced contraction of aortic strips was inhibited by piceatannol, PD98059, and SB203580, inhibitors of Syk, extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 mitogen-activated protein kinase (MAPK), respectively. Piceatannol also attenuated high K+-induced contraction. ET-1 dose-dependently enhanced the activity of Syk and this was inhibited by piceatannol in both rat aortic strip and rat aortic smooth muscle cells. The phosphorylation of p38 MAPK and heat shock protein 27 (HSP27), but not that of ERK1/2, in response to ET-1 was inhibited by both piceatannol and SB203580. These results suggest that Syk may play an important role in the regulation of aortic smooth muscle contraction induced by ET-1, which may be mediated by the p38 MAPK/HSP27 signaling pathway.

【 授权许可】

Unknown