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Activation of p38 MAPK Is Involved in Endothelin-1-stimulated COX-2 Expression in Cultured Feline Esophageal Smooth Muscle Cells  

Song, Hyun Ju (Department of Pharmacology, College of Pharmacy, Chung Ang University)
Min, Young Sil (Department of Pharmacology, College of Pharmacy, Chung Ang University)
Shin, Chang Yell (Department of Pharmacology, College of Pharmacy, Chung Ang University)
Jeong, Ji Hoon (Department of Pharmacology, School of Medicine, Chung Ang University)
Sohn, Uy Dong (Department of Pharmacology, College of Pharmacy, Chung Ang University)
Publication Information
Molecules and Cells / v.22, no.1, 2006 , pp. 44-50 More about this Journal
Abstract
We investigated the possible role of p38 MAPK and $ET_B$ receptors in ET-1 induction of cyclooxygenase-2 (COX-2) and prostaglandin $E_2$ ($PGE_2$) in cultured feline esophageal smooth muscle cells (ESMC). Confluent layers of ESMC were stimulated with 10 nM ET-1 and expression of COX-1 and COX-2, involvement of receptors, and activation of p38 MAPK, were examined by Western blot analysis. Levels of $PGE_2$ induced by ET-1 were measured by Elisa. Using $ET_A$and $ET_B$ antagonists (BQ-123 and BQ-788, respectively), the contribution of the ET receptors to COX-1 and COX-2 expression induced by ET-1 was determined. Western blot analysis revealed that treatment of ESMC with ET-1 resulted in transient expression of COX-2 and activation of p38 MAPK. Activation of p38 MAPK was maximal after 1 h. SB202190, a p38 MAPK inhibitor, reduced expression of COX-2, but not COX-1. ET-1-induced release of $PGE_2$ was also blocked by SB202190. COX-2 expression was upregulated only via the $ET_B$ receptor, and COX-1 expression was not affected by either antagonist. Taken together, our data suggest that ET-1 causes p38 MAPK-dependent expression of COX-2 by interacting with $ET_B$ receptors on ESMC.
Keywords
COX; Esophageal Smooth Muscle Cells; ET-1; $ET_B$ Receptor; p38 MAPK; $PGE_2$;
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Times Cited By KSCI : 2  (Citation Analysis)
Times Cited By Web Of Science : 6  (Related Records In Web of Science)
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