Induction of pacemaker currents by DA-9701, a prokinetic agent, in interstitial cells of Cajal from murine small intestine

• Published in: Molecules and cells 2009, 27(3), , pp.307-312
• Main Authors: Choi, S. (Chosun University, Gwangju, Republic of Korea), Choi, J.J. (Daejeon University, Daejeon, Republic of Korea), Jun, J.Y. (Chosun University, Gwangju, Republic of Korea), Koh, J.W. (Chosun University, Gwangju, Republic of Korea), Kim, S.H. (Chosun University, Gwangju, Republic of Korea), Kim, D.H. (Daejeon University, Daejeon, Republic of Korea), Pyo, M.Y. (Sookmyung Women's University, Seoul, Republic of Korea), Choi, S.Z. (Dong-A Pharm. Co., Ltd., Research and Development Center, Yongin, Republic of Korea), Son, J.P. (Dong-A Pharm. Co., Ltd., Research and Development Center, Yongin, Republic of Korea), Lee, I.K. (Dong-A Pharm. Co., Ltd., Research and Development Center, Yongin, Republic of Korea), Son, M.W. (Dong-A Pharm. Co., Ltd., Research and Development Center, Yongin, Republic of Korea), Jin, M.R. (Daejeon University, Daejeon, Republic of Korea), E-mail: [e-mail]
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Calcium - metabolism; Cell Biology; CELLS; CELLULE; CELULAS; Corydalis Tuber; DA-9701; Female; Flufenamic Acid - pharmacology; Gastrointestinal Agents - pharmacology; Gastrointestinal Motility - physiology; ICC; Intestine, Small - cytology; Intestine, Small - drug effects; Intestine, Small - metabolism; Life Sciences; Male; Membrane Potentials - drug effects; Mice; Mice, Inbred BALB C; Niflumic Acid - pharmacology; pacemaker currents; Patch-Clamp Techniques; Pharbitis Semen; Plant Preparations - pharmacology; prokinetics; Type C Phospholipases - antagonists & inhibitors; Type C Phospholipases - metabolism; 생물학
• ISSN: 1016-8478; 0219-1032
• DOI: 10.1007/s10059-009-0039-6

The interstitial cells of Cajal (ICC) are pacemaking cells required for gastrointestinal motility. The possibility of whether DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber, modulates pacemaker activities in the ICC was tested using the whole cell patch clamp technique. DA-9701 produced membrane depolarization and increased tonic inward pacemaker currents in the voltage-clamp mode. The application of flufenamic acid, a non-selective cation channel blocker, but not niflumic acid, abolished the generation of pacemaker currents induced by DA-9701. Pretreatment with a Ca²+-free solution and thapsigargin, a Ca²+-ATPase inhibitor in the endoplasmic reticulum, abolished the generation of pacemaker currents. In addition, the tonic inward currents were inhibited by U-73122, an active phospholipase C inhibitor, but not by GDP-β-S, which permanently binds G-binding proteins. Furthermore, the protein kinase C inhibitors, chelerythrine and calphostin C, did not block the DA-9701-induced pacemaker currents. These results suggest that DA-9701 might affect gastrointestinal motility by the modulation of pacemaker activity in the ICC, and the activation is associated with the non-selective cationic channels via external Ca²+ influx, phospholipase C activation, and Ca²+ release from internal storage in a G protein-independent and protein kinase C-independent manner.