title: Induction of pacemaker currents by DA-9701, a prokinetic agent, in interstitial cells of Cajal from murine small intestine.
abstract: 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-beta-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.
authors.affiliation: Department of Physiology, College of Medicine, Chosun University, Gwangju 501-759, Korea.
authors.forename: Seok
authors.initials: S
authors.lastname: Choi
authors.forename: Jeong June
authors.initials: JJ
authors.lastname: Choi
authors.forename: Jae Yeoul
authors.initials: JY
authors.lastname: Jun
authors.forename: Jae Woong
authors.initials: JW
authors.lastname: Koh
authors.forename: Sang Hun
authors.initials: SH
authors.lastname: Kim
authors.forename: Dong Hee
authors.initials: DH
authors.lastname: Kim
authors.forename: Myoung-Yun
authors.initials: MY
authors.lastname: Pyo
authors.forename: Sangzin
authors.initials: S
authors.lastname: Choi
authors.forename: Jin Pub
authors.initials: JP
authors.lastname: Son
authors.forename: Inki
authors.initials: I
authors.lastname: Lee
authors.forename: Miwon
authors.initials: M
authors.lastname: Son
authors.forename: Mirim
authors.initials: M
authors.lastname: Jin