title: Lipopolysaccharide-induced intestinal motility disturbances are mediated by c-Jun NH2-terminal kinases.
abstract: BACKGROUND
  Lipopolysaccharide (LPS) is a causative agent of sepsis. Many alterations, such as intestinal motility disturbances, have been attributed to LPS.
  
  
  OBJECTIVE
  Here we investigated the role of c-Jun NH(2)-terminal kinases (JNK) in the effect of LPS on intestinal motility, the oxidative stress status and the cyclooxygenese-2 (COX-2) expression.
  
  
  METHODS
  Rabbits were injected with either (1) saline, (2) LPS, (3) SP600125, a specific JNK inhibitor, or (4) SP600125+LPS. Duodenal contractility was studied in an organ bath. The formation of products of oxidative damage to proteins (carbonyls) and lipids [malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA)] was quantified by spectrophotometry in the intestine and plasma. The protein expression of p-JNK, total JNK, and COX-2 was measured by Western blot, and p-JNK was localized by immunohistochemistry.
  
  
  RESULTS
  LPS decreased the contractions evoked by acetylcholine and prostaglandin E(2) and KCl-induced contractions. LPS increased phospho-JNK and COX-2 expressions and the levels of carbonyls and MDA+4-HDA. SP600125 blocked the effect of LPS on the acetylcholine, prostaglandin E(2), and KCl-induced contractions, the levels of carbonyls and MDA+4-HDA, and the p-JNK and COX-2 expressions. p-JNK was detected in the smooth muscle cells of duodenum.
  
  
  CONCLUSIONS
  Our results suggest that JNK is involved in the mechanism of action of LPS in the intestine.
authors.affiliation: Departamento de Farmacología y Fisiología, Unidad de Fisiología, Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Gonzalo
authors.forename: Laura
authors.initials: L
authors.lastname: Grasa
authors.forename: María Pilar
authors.initials: MP
authors.lastname: Árruebo
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Plaza
authors.forename: María Divina
authors.initials: MD
authors.lastname: Murillo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004386:Duodenum / Q000187:drug effects* / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D008070:Lipopolysaccharides; D008315:Malondialdehyde; D051546:Cyclooxygenase 2; D048031:JNK Mitogen-Activated Protein Kinases