title: The mechanism of MAP kinase activation under acidic condition in feline esophageal smooth muscle cells.
abstract: Reflux esophagitis results from repeated exposure of the esophagus to acidic gastric juice or bile-containing duodenal contents. In Barrett's adenocarcinoma, acid increases proliferation via ERK and p38 MAPK activation. This study was focused on determination of the mechanism(s) underlying MAPKs (ERK 1/2, p38 MAPK, and JNK) activation induced by acidic medium at pH 4 in normal feline primary cultured esophageal smooth muscle cells (FESMCs). We detected ERK 1/2 and p38 MAPK phosphorylation after exposure to pH 4 or neutral media in the presence or absence of several inhibitors and quantified the MAPK levels using western blotting analysis and densitometry. Acidic medium markedly increased the phosphorylation of ERK 1/2 and p38 MAPK within 10 min. Acid-induced ERK 1/2 and p38 MAPK activation was inhibited by pertussis toxin (PTX-sensitive G(i/o) protein inhibitor), DEDA (phospholipase (PL) A(2) inhibitor), ρCMB (PLD inhibitor), GF109203X (protein kinase C (PKC) inhibitor) and D609 (phosphatidylcholine-specific PLC inhibitor). But, genistein (tyrosine kinase inhibitor), forskolin (adenylate cyclase activator) and U73122 (phosphatidylinositol-specific PLC inhibitor) had no effect on acid-induced ERK1/2 and p38 MAPK activation. These findings indicate that the activation of ERK 1/2 and p38 MAPK pathways by acidic conditions, at least in part, may be mediated by activation of the G(i/o) protein coupled receptors, PC-PLC, PLD, PLA(2), and PKC in FESMCs.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Park
authors.forename: Young Ju
authors.initials: YJ
authors.lastname: Lee
authors.forename: Youngsil
authors.initials: Y
authors.lastname: Min
authors.forename: Hak Rim
authors.initials: HR
authors.lastname: Kim
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jeong
authors.forename: Uy Dong
authors.initials: UD
authors.lastname: Sohn
mesh_terms: D000143:Acids; D000818:Animals; D015153:Blotting, Western; D002415:Cats; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004789:Enzyme Activation; D004947:Esophagus / Q000166:cytology* / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009124:Muscle Proteins / Q000737:chemistry; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D037342:Pertussis Toxin / Q000494:pharmacology; D064801:Phospholipase A2 Inhibitors; D010739:Phospholipase D / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000143:Acids; D009124:Muscle Proteins; D064801:Phospholipase A2 Inhibitors; D005576:Colforsin; D037342:Pertussis Toxin; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D010739:Phospholipase D