title: Inhibition of pacemaker activity in interstitial cells of Cajal by LPS via NF-κB and MAP kinase.
abstract: OBJECTIVE
  To investigate lipopolysaccharide (LPS) related signal transduction in interstitial cells of Cajal (ICCs) from mouse small intestine.
  
  
  METHODS
  For this study, primary culture of ICCs was prepared from the small intestine of the mouse. LPS was treated to the cells prior to measurement of the membrane currents by using whole-cell patch clamp technique. Immunocytochemistry was used to examine the expression of the proteins in ICCs.
  
  
  RESULTS
  LPS suppressed the pacemaker currents of ICCs and this could be blocked by AH6809, a prostaglandin E2-EP2 receptor antagonist or NG-Nitro-L-arginine Methyl Ester, an inhibitor of nitric oxide (NO) synthase. Toll-like receptor 4, inducible NO synthase or cyclooxygenase-2 immunoreactivity by specific antibodies was detected on ICCs. Catalase (antioxidant agent) had no action on LPS-induced action in ICCs. LPS actions were blocked by nuclear factor κB (NF-κB) inhibitor, actinomycin D (a gene transcription inhibitor), PD 98059 (a p42/44 mitogen-activated protein kinases inhibitor) or SB 203580 [a p38 mitogen-activated protein kinases (MAPK) inhibitor]. SB 203580 also blocked the prostaglandin E2-induced action on pacemaker currents in ICCs but not NO.
  
  
  CONCLUSIONS
  LPS inhibit the pacemaker currents in ICCs via prostaglandin E2- and NO-dependent mechanism through toll-like receptor 4 and suggest that MAPK and NF-κB are implicated in these actions.
authors.affiliation: Department of Physiology, College of Medicine, Chosun University, Gwangju 501-759, South Korea.
authors.forename: Dong Chuan
authors.initials: DC
authors.lastname: Zuo
authors.forename: Seok
authors.initials: S
authors.lastname: Choi
authors.forename: Pawan Kumar
authors.initials: PK
authors.lastname: Shahi
authors.forename: Man Yoo
authors.initials: MY
authors.lastname: Kim
authors.forename: Chan Guk
authors.initials: CG
authors.lastname: Park
authors.forename: Young Dae
authors.initials: YD
authors.lastname: Kim
authors.forename: Jun
authors.initials: J
authors.lastname: Lee
authors.forename: In Yeoup
authors.initials: IY
authors.lastname: Chang
authors.forename: Insuk
authors.initials: I
authors.lastname: So
authors.forename: Jae Yeoul
authors.initials: JY
authors.lastname: Jun
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001683:Biological Clocks / Q000187:drug effects*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D056885:Interstitial Cells of Cajal / Q000187:drug effects* / Q000201:enzymology; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D010507:Periodicity; D061251:Primary Cell Culture; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000187:drug effects / Q000378:metabolism
chemical_list: D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone
keywords: Interstitial cells of Cajal; Lipopolysaccharide; Mitogen-activated protein kinases; Nuclear factor κB; Small intestine