title: Effects of Dangkwisoo‑san, a traditional herbal medicine for treating pain and blood stagnation, on the pacemaker activities of cultured interstitial cells of Cajal.
abstract: The interstitial cells of Cajal (ICCs) are the pacemaker cells in the gastrointestinal (GI) tract. In the present study, the effects of Dangkwisoo‑san (DS) on pacemaker potentials in cultured ICCs from the small intestine of the mouse were investigated. The whole‑cell patch‑clamp configuration was used to record pacemaker potentials from cultured ICCs and the increase in intracellular Ca2+ concentration ([Ca2+i) was analyzed in cultured ICCs using fura‑2‑acetoxymethyl ester. The generation of pacemaker potentials in the ICCs was observed. DS produced pacemaker depolarizations in a concentration dependent manner in current clamp mode. The 4‑diphenylacetoxy‑N‑methyl‑piperidine methiodide muscarinic M3 receptor antagonist inhibited DS‑induced pacemaker depolarizations, whereas methoctramine, a muscarinic M2 receptor antagonist, did not. When guanosine 5'‑[β‑thio] diphosphate (GDP‑β‑S; 1 mM) was in the pipette solution, DS marginally induced pacemaker depolarizations, whereas low Na+ solution externally eliminated the generation of pacemaker potentials and inhibited the DS‑induced pacemaker depolarizations. Additionally, the nonselective cation channel blocker, flufenamic acid, inhibited the DS‑induced pacemaker depolarizations. Pretreatment with Ca2+‑free solution and thapsigargin, a Ca2+‑ATPase inhibitor in the endoplasmic reticulum, also eliminated the generation of pacemaker currents and suppressed the DS‑induced pacemaker depolarizations. In addition, [Ca2+]i analysis revealed that DS increased [Ca2+]i. These results suggested that DS modulates pacemaker potentials through muscarinic M3 receptor activation in ICCs by G protein‑dependent external and internal Ca2+ regulation and external Na+. Therefore, DS were observed to affect intestinal motility through ICCs.
authors.affiliation: Department of Neurosurgery, Pusan National University, Yangsan Hospital, Yangsan, Gyeongsangnam-do 626‑870, Republic of Korea.
authors.forename: Soon-Ki
authors.initials: SK
authors.lastname: Sung
authors.affiliation: Department of Neurosurgery, Pusan National University, Yangsan Hospital, Yangsan, Gyeongsangnam-do 626‑870, Republic of Korea.
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do 626‑870, Republic of Korea.
authors.forename: Tae Seok
authors.initials: TS
authors.lastname: Ahn
authors.affiliation: Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do 626‑870, Republic of Korea.
authors.forename: Noo Ri
authors.initials: NR
authors.lastname: Hong
authors.affiliation: Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do 626‑870, Republic of Korea.
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Park
authors.affiliation: Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do 626‑870, Republic of Korea.
authors.forename: Young Kyu
authors.initials: YK
authors.lastname: Kwon
authors.affiliation: Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do 626‑870, Republic of Korea.
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D003959:Diamines / Q000494:pharmacology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D056885:Interstitial Cells of Cajal / Q000187:drug effects*; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010146:Pain / Q000188:drug therapy*; D008517:Phytotherapy; D010880:Piperidines / Q000494:pharmacology; D010946:Plants, Medicinal / Q000009:adverse effects; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D013873:Thionucleotides / Q000378:metabolism
chemical_list: D003959:Diamines; D010880:Piperidines; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D019284:Thapsigargin; C023427:guanosine 5'-O-(2-thiodiphosphate); C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D000252:Calcium-Transporting ATPases; C054938:methoctramine