Effects of Imatinib Mesylate in Interstitial Cells of Cajal from Murine Small Intestine
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概要
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The interstitial cells of Cajal (ICCs) are pacemakers in the gastrointestinal tract. The possibility of whether imatinib mesylate, a Kit receptor tyrosine kinase inhibitor, modulates pacemaker activities in the ICC was examined using the whole cell patch clamp technique. Imatinib decreased the amplitude of pacemaker potentials in a dose-dependent manner in current-clamp mode. Because the effects of imatinib on pacemaker potentials were the same as those of pinacidil, we examined the effect of glibenclamide on ICC exposed to imatinib. The effects of imatinib on pacemaker potentials were blocked by glibenclamide. To see whether the production of prostaglandins (PGs) is involved in the inhibitory effect of imatinib on pacemaker potentials, we tested the effects of naproxen (a non-selective cyclooxygenase inhibitor) and AH6809 (a prostaglandin EP1 and EP2 receptor antagonist). Naproxen and AH6809 blocked the inhibitory effects of imatinib on ICC. Butaprost (an EP2 receptor agonist) showed the actions on pacemaker potentials in the same manner as imatinib. However, SC 19220 (an EP1 receptor antagonist) has no effects. To investigate the involvement of cAMP and protein kinase A (PKA) in the effects of imatinib on ICC, SQ 22536 (an inhibitor of adenylate cyclase) and mPKAI (an inhibitor of myristoylated PKA) were used. Both SQ-22536 and mPKAI blocked the imatinib-mediated inhibition of pacemaker potentials. However, the protein kinase C (PKC) inhibitors did not block the imatinib-mediated inhibition of pacemaker potentials. These results indicate that imatinib inhibits the pacemaker potentials of ICC by activating ATP-sensitive K+ channels and PKA-dependent, PKC-independent manner.
著者
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So Insuk
Department of Physiology, Seoul National University College of Medicine
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Kim Byung
Division of Cardiology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan Univ
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So Insuk
Department Of Physiology And Biophysics Seoul National University College Of Medicine
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Chae Han
Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicin
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Kwon Young
Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicin
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Choi Seok
Department of Physiology, Chosun University College of Medicine
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Jun Jae
Department of Physiology, Chosun University College of Medicine
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Jeon Ju-Hong
Department of Physiology, Seoul National University College of Medicine
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Kim Seon
Center for Bio-Artificial Muscle and Department of Biomedical Engineering, Hanyang University
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Kim Seon
Center For Bio-artificial Muscle And Dep. Of Biomedical Engineering Hanyang Univ.
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Jun Jae
Department Of Internal Medicine Kyungpook National University Hospital
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Kim Byung
Division Of Breast And Endocrine Surgery Hallym University Sacred Heart Hospital College Of Medicine
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Choi Seok
Department Of Information And Communications Kwangju Institute Of Science And Technology
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Chae Han
Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine
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Kwon Young
Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine
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Kim Byung
Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine
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