title: Inhibition of gut pacemaker cell formation from mouse ES cells by the c-kit inhibitor.
abstract: Using an embryoid body (EB) culture system, we developed a functional organ-like cluster, a "gut", from mouse embryonic stem (ES) cells (ES gut). Each ES gut exhibited various types of spontaneous movements. In these spontaneously contracting ES guts, dense distributions of interstitial cells of Cajal (ICC) (c-kit, a transmembrane receptor that has tyrosine kinase activity, positive cells; gut pacemaker cells) and smooth muscle cells were discernibly identified. By adding Glivec 10(-5)M, a tyrosine kinase receptor c-kit inhibitor, only during EB formation, we for the first time succeeded in suppressing in vitro formation of ICC in the ES gut. The ES gut without ICC did not exhibit any movements. However, it appeared that Glivec 10(-6)-10(-7)M rather increased number of ES guts with spontaneous movements associated with increase of intracellular Ca(2+) concentration ([Ca(2+)](i)). These results suggest ICC is critical for in vitro formation of ES guts with spontaneous movements.
authors.affiliation: Department of Physiology II, Nara Medical University, School of Medicine, Kashihara, Nara, Japan. mtakaki@naramed-u.ac.jp
authors.forename: Miyako
authors.initials: M
authors.lastname: Takaki
authors.forename: Hiromi
authors.initials: H
authors.lastname: Misawa
authors.forename: Juichiro
authors.initials: J
authors.lastname: Shimizu
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuniyasu
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Horiguchi
mesh_terms: D000818:Animals; D001549:Benzamides; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D020541:Coiled Bodies / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D007422:Intestines / Q000166:cytology*; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D010879:Piperazines / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D013997:Time Factors
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; D002118:Calcium