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

• Published in: Journal of Pharmacological Sciences 2007, Vol.103(4), pp.427-433
• Main Authors: Lee, Hwan Myung, Won, Kyung-Jong, Kim, Junghwan, Park, Hyo-Jun, Kim, Hyo Jin, Roh, Hui Yul, Lee, So Hee, Lee, Chang-Kwon, Kim, Bokyung
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Aorta - cytology; Aorta - drug effects; Aorta - physiology; Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors; Cells, Cultured; contraction; Dose-Response Relationship, Drug; endothelin-1; Endothelin-1 - pharmacology; Enzyme Inhibitors - pharmacology; Flavonoids - pharmacology; Imidazoles - pharmacology; Immunoblotting; Immunoprecipitation; In Vitro Techniques; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors; Intracellular Signaling Peptides and Proteins - metabolism; Male; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; p38 mitogen-activated protein kinase (MAPK); p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation - drug effects; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - metabolism; Pyridines - pharmacology; rat aortic smooth muscle cell (RASMC); Rats; Rats, Sprague-Dawley; spleen tyrosine kinase (Syk); Stilbenes - pharmacology; Syk Kinase; Vasoconstriction - drug effects
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.FP0070039

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.