Activation of p38 MAPK is involved in endothelin-1-stimulated COX-2 expression in cultured Feline esophageal smooth muscle cells.
We investigated the possible role of p38 MAPK and ETB receptors in ET-1 induction of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) 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 PGE2 induced by ET-1 were measured by Elisa. Using ETA and ETB 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 PGE2 was also blocked by SB202190. COX-2 expression was upregulated only via the ETB 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 ETB receptors on ESMC.
Song
Hyun Ju
HJ
Department of Pharmacology, College of Pharmacy, Chung Ang University, Seoul 156-756, Korea.
Min
Young Sil
YS
Shin
Chang Yell
CY
Jeong
Ji Hoon
JH
Sohn
Uy Dong
UD
D000818:Animals; D015153:Blotting, Western; D002415:Cats; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D019332:Endothelin-1 / Q000502:physiology*; D004789:Enzyme Activation; D004947:Esophagus / Q000166:cytology*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044022:Receptor, Endothelin A / Q000187:drug effects / Q000502:physiology; D044023:Receptor, Endothelin B / Q000187:drug effects / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D019332:Endothelin-1; D007093:Imidazoles; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D011725:Pyridines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C086539:BQ 788; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C072247:cyclo(Trp-Asp-Pro-Val-Leu)