title: Effects ofPrunus mumeSiebold & Zucc. in the pacemaking activity of interstitial cells of Cajal in murine small intestine.
abstract: Interstitial cells of Cajal (ICCs) function as pacemaker cells in the gastrointestinal (GI) tract and therefore, serve an important role in regulating GI motility. The effects of a species of plum (Prunus mumeSiebold & Zucc.) on cultured ICC cluster-induced pacemaker potentials in the mouse small intestine were investigated, and the effects of a methanolic extract ofPrunus mume(m-PM) on ICC pacemaker activities were examined using the whole-cell patch-clamp technique. ICC pacemaker membrane potentials were depolarized by m-PM in a concentration dependent manner in current clamp mode. 4-Diphenylacetoxy-N-methyl-piperidine methiodide, which is a muscarinic 3 (M3) receptor antagonist, was able to block m-PM-induced pacemaker potential increases, whereas methoctramine, which is a muscarinic 2 (M2) receptor antagonist, was not. When 1 mM guanosine diphosphate β-5 was present in the pipette solution, m-PM induced slight pacemaker depolarization. Following pretreatment in bath solution of Ca2+-free solution or a Ca2+-ATPase inhibitor in endoplasmic reticulum, the pacemaker currents were inhibited. Furthermore, pretreatment with PD98059, SB203580 or SP600125, which is a c-jun NH2-terminal kinase inhibitor, blocked m-PM-induced ICC potential depolarization. Furthermore, m-PM inhibited transient receptor potential melastatin (TRPM) 7 channels, but did not affect Ca2+-activated Cl-channels. These results suggest that m-PM is able to modulate pacemaker potentials through the muscarinic M3receptor, via G-protein and external and internal Ca2+, in a mitogen-activated protein kinase and TRPM7-dependent manner. Therefore, m-PM may provide a basis for the development of a novel gastroprokinetic agent.
authors.affiliation: Department of Neurosurgery, Pusan National University Yangsan Hospital, Yangsan, Gyeongsangnam 50612, Republic of Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Gyeongsangnam 50612, Republic of Korea.
authors.forename: Sang Weon
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, Pusan National University Yangsan Hospital, Yangsan, Gyeongsangnam 50612, Republic of Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Gyeongsangnam 50612, Republic of Korea.
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Division of Pharmacology, Pusan National University School of Korean Medicine, Yangsan, Gyeongsangnam 50612, Republic of Korea.
authors.forename: Hyungwoo
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Physiology, Gachon University College of Medicine, Incheon, Gyeonggi 22332, Republic of Korea.
authors.forename: Dongki
authors.initials: D
authors.lastname: Yang
authors.affiliation: Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan, Gyeongsangnam 50612, Republic of Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan, Gyeongsangnam 50612, Republic of Korea.
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Kim
keywords: Prunus mume Siebold & Zucc.; gastrointestinal tract; interstitial cells of Cajal; plum