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Effects of Prunus mume Siebold & Zucc in the pacemaking activity of interstitial cells of Cajal in murine small intestine #MMPMID28123510
Lee SW; Kim SJ; Kim H; Yang D; Kim HJ; Kim BJ
Exp Ther Med 2017[Jan]; 13 (1): 327-334 PMID28123510show ga
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 mume Siebold & Zucc.) on cultured ICC cluster-induced pacemaker potentials in the mouse small intestine were investigated, and the effects of a methanolic extract of Prunus 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 (M(3)) receptor antagonist, was able to block m-PM-induced pacemaker potential increases, whereas methoctramine, which is a muscarinic 2 (M(2)) receptor antagonist, was not. When 1 mM guanosine diphosphate beta-5 was present in the pipette solution, m-PM induced slight pacemaker depolarization. Following pretreatment in bath solution of Ca(2+)-free solution or a Ca(2+)-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 Ca(2+)-activated Cl(-) channels. These results suggest that m-PM is able to modulate pacemaker potentials through the muscarinic M(3) receptor, via G-protein and external and internal Ca(2+), 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.