1. Regulatory Roles of Endogenous Mitogen-Activated Protein Kinases and Tyrosine Kinases in the Pacemaker Activity of Colonic Interstitial Cells of Cajal
- Author
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Dong-Hoon Shin, Il Koo Park, Insuk So, Jisun Na, Han Yi Jiao, Man Woo Kim, Chan Guk Park, Seok Choi, Mi Jeong Lee, Seok Won Kim, and Jae Yeoul Jun
- Subjects
Colon ,Pyridines ,Morpholines ,MAPK7 ,Protein tyrosine phosphatase ,Naphthalenes ,Receptor tyrosine kinase ,Membrane Potentials ,Mice ,symbols.namesake ,Intestine, Small ,Animals ,Cells, Cultured ,Anthracenes ,Benzophenanthridines ,Flavonoids ,Pharmacology ,biology ,Chemistry ,Imidazoles ,General Medicine ,Smooth muscle contraction ,Protein-Tyrosine Kinases ,Interstitial Cells of Cajal ,Genistein ,Interstitial cell of Cajal ,Cell biology ,Rifabutin ,Chromones ,Mitogen-activated protein kinase ,symbols ,biology.protein ,Mitogen-Activated Protein Kinases ,Tyrosine kinase ,Proto-oncogene tyrosine-protein kinase Src - Abstract
Background and Purpose: 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.
- Published
- 2015