Effects of Dangkwisoo­san, a traditional herbal medicine for treating pain and blood stagnation, on the pacemaker activities of cultured interstitial cells of Cajal.

The interstitial cells of Cajal (ICCs) are the pacemaker cells in the gastrointestinal (GI) tract. In the present study, the effects of Dangkwisoo­san (DS) on pacemaker potentials in cultured ICCs from the small intestine of the mouse were investigated. The whole­cell patch­clamp 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 fura­2­acetoxymethyl 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 4­diphenylacetoxy­N­methyl­piperidine methiodide muscarinic M3 receptor antagonist inhibited DS­induced pacemaker depolarizations, whereas methoctramine, a muscarinic M2 receptor antagonist, did not. When guanosine 5'­[ß­thio] diphosphate (GDP­ß­S; 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 DS­induced pacemaker depolarizations. Additionally, the nonselective cation channel blocker, flufenamic acid, inhibited the DS­induced 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 DS­induced 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 protein­dependent external and internal Ca2+ regulation and external Na+. Therefore, DS were observed to affect intestinal motility through ICCs.

Effects of Schisandra chinensis extract on gastrointestinal motility in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis (Turcz.) Baill. (SC) continues to be used as a traditional folk medicine in Asia, especially for the treatment of gastrointestinal (GI) disorders related to gastritis, diarrhea, enterocolitis and abnormal GI motility. AIM OF THE STUDY: Because GI disorders, especially abnormal GI motility, are major lifelong problems, we investigated the effects of SC on the pacemaker activity of the interstitial cells of Cajal (ICCs) in murine small intestine and GI motility. MATERIALS AND METHODS: Enzymatic digestions were used to dissociate ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record potentials generated by cultured ICCs. In vivo effects of SC on GI motility were investigated by measuring the intestinal transit rate (ITR) of Evans blue in normal and GI motility dysfunction mice. RESULTS: SC extracts depolarized the membrane potentials of ICCs in a dose dependent manner. Pretreatment with Ca(2+) free solution or thapsigargin (a Ca(2+)-ATPase inhibitor in the endoplasmic reticulum) abolished the generation of pacemaker potentials by ICCs, and under these conditions, SC extract did not depolarize the membrane potentials of ICCs. In addition, membrane depolarizations were inhibited by intracellular GDPßS and by U-73122 (an active phospholipase C (PLC) inhibitor). In normal mice, ITRs were significantly increased by SC extract (0.1-1g/kg, intragastrically (i.g.)) in a dose dependent manner. Also, SC extract significantly recovered the GI motility dysfunctions in acetic acid (AA)-injected and streptozotocin (STZ)-induced diabetic mice, which are the GI motility animal models. MATERIALS AND METHODS: SC extract modulates pacemaker potentials in ICCs in a dose dependent manner via external and internal Ca(2+) regulations, and via G protein and the PLC pathway. In addition, SC extract increased ITRs in normal and abnormal GI motility mice models. This study shows that SC extract offers a basis for the development of a prokinetic agent that prevents or alleviates GI motility dysfunctions.

Effects of traditional Chinese herbal medicine San-Huang-Xie-Xin-Tang on gastrointestinal motility in mice.

AIM: To investigate the effects of San-Huang-Xie-Xin-Tang (SHXXT), a herbal product used in traditional Chinese medicine, on gastrointestinal (GI) motility in mice. METHODS: The in vivo effects of SHXXT on GI motility were investigated by measuring the intestinal transit rates (ITRs) using Evans blue in normal mice and in mice with experimentally induced GI motility dysfunction (GMD). RESULTS: In normal ICR mice, ITRs were significantly and dose-dependently increased by SHXXT (0.1-1 g/kg). GMD was induced by injecting acetic acid or streptozotocin intraperitoneally. The ITRs of GMD mice were significantly reduced compared to normal mice, and these reductions were significantly and dose-dependently inhibited by SHXXT (0.1-1 g/kg). CONCLUSION: These results suggest that SHXXT is a novel candidate for the development of a prokinetic agent that may prevent or alleviate GMD.