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KMID : 0578320090270030307
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Molecules and Cells
2009 Volume.27 No. 3 p.307 ~ p.312
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Induction of Pacemaker Currents by DA-9701, a Prokinetic Agent, in Interstitial Cells of Cajal from Murine Small Intestine
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Choi Seok
Choi Jeong-June
Jun Jae-Yeoul
Koh Jae-Woong
Kim Sang-Hun
Kim Dong-Hee
Pyo Myoung-Yun
Choi Sang-Zin
Son Jin-Pub
Lee In-Ki
Son Mi-Won
Jin Mi-Rim
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Abstract
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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-??S, which permanently binds G-binding proteins. Furthermore, the protein kinase C inhibitors, chel-erythrine 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 activa-tion, and Ca2+ release from internal storage in a G pro-tein-independent and protein kinase C-independent manner.
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KEYWORD
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Corydalis Tuber, DA-9701, ICC, pacemaker currents, Pharbitis Semen, prokinetics
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