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 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 (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 M3 receptor, 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.
journal_name
Exp Ther Medjournal_title
Experimental and therapeutic medicineauthors
Lee SW,Kim SJ,Kim H,Yang D,Kim HJ,Kim BJdoi
10.3892/etm.2016.3963subject
Has Abstractpub_date
2017-01-01 00:00:00pages
327-334issue
1eissn
1792-0981issn
1792-1015pii
ETM-0-0-3963journal_volume
13pub_type
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