title: Regulatory Roles of Endogenous Mitogen-Activated Protein Kinases and Tyrosine Kinases in the Pacemaker Activity of Colonic Interstitial Cells of Cajal.
abstract: OBJECTIVE
  Mitogen-activated protein (MAP) and tyrosine kinases play an important role in regulating smooth muscle contraction of the gastrointestinal (GI) tract. Interstitial cells of Cajal (ICCs) are pacemaker cells that regulate GI smooth muscle activity. Thus, the role of MAP and tyrosine kinases on the pacemaker potentials of colonic ICCs was investigated.
  
  
  METHODS
  Cultured ICCs were prepared from mice colons, and their pacemaker potentials were recorded using whole-cell patch clamping.
  
  
  RESULTS
  In current-clamping mode, colonic ICCs displayed spontaneous pacemaker potentials. SB203580 (a p38 MAP kinase inhibitor), SP600125 (a c-jun NH2-terminal kinase (JNK) inhibitor), genistein and herbimycin A (tyrosine kinase inhibitors) blocked the generation of pacemaker potentials. However, PD98059 (a p42/44 MAP kinase inhibitor) had no effects on pacemaker potentials. LY-294002 (phosphoinositide 3-kinase inhibitor) also reduced the pacemaker potential frequency but calphostin C and chelerythrine (protein kinase C inhibitors) had no effects. However, PD98059, SB203589, SP600125, genistein, herbimycin A, LY-294002, and calphostin C had no effect on normal pacemaker activity in small intestinal ICCs.
  
  
  CONCLUSIONS
  Endogenous p38 MAP kinases, JNKs, tyrosine kinases, and PI3-kinases participate in the generation of pacemaker potentials in colonic ICCs but not in ICCs of the small intestine.
authors.affiliation: Department of Physiology, College of Medicine, Gwangju, Korea.
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Shin
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Lee
authors.forename: Han Yi
authors.initials: HY
authors.lastname: Jiao
authors.forename: Seok
authors.initials: S
authors.lastname: Choi
authors.forename: Man Woo
authors.initials: MW
authors.lastname: Kim
authors.forename: Chan Guk
authors.initials: CG
authors.lastname: Park
authors.forename: Jisun
authors.initials: J
authors.lastname: Na
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Il Koo
authors.initials: IK
authors.lastname: Park
authors.forename: Insuk
authors.initials: I
authors.lastname: So
authors.forename: Jae Yeoul
authors.initials: JY
authors.lastname: Jun
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D053119:Benzophenanthridines / Q000494:pharmacology; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D056885:Interstitial Cells of Cajal / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D007421:Intestine, Small / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000873:Anthracenes; D053119:Benzophenanthridines; D002867:Chromones; D005419:Flavonoids; D007093:Imidazoles; D009025:Morpholines; D009281:Naphthalenes; D011725:Pyridines; C432165:pyrazolanthrone; D017828:Rifabutin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C020754:herbimycin; D019833:Genistein; C016299:chelerythrine; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; C058819:calphostin C; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one