Regulation of the pacemaker activities in cultured interstitial cells of Cajal by Citrus unshiu peel extracts

Abstract

The Citrus unshiu peel has been widely used for the treatment of gastrointestinal (GI) disorders in Eastern traditional medicine. The present study aimed to investigate the effects of Citrus unshiu peel extract (CPE) on the pacemaker activity of the GI tract in cultured interstitial cells of Cajal (ICCs) derived from the mouse small intestine. The whole‑cell patch‑clamp configuration was used to record pacemaker potentials. In current clamp mode, exposure to CPE caused membrane pacemaker depolarization in a concentration‑dependent manner. In the presence of the muscarinic M2 receptor antagonist, methoctramine, CPE induced membrane pacemaker depolarization, whereas treatment with the muscarinic M3 receptor antagonist, 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide, inhibited CPE‑induced responses. When the pipette solution contained guanosine 5'-(β-thio) diphosphate trilithium salt (1 mM), CPE marginally induced membrane pacemaker depolarization. In addition, CPE‑induced membrane pacemaker depolarization was inhibited following exposure to the active phospholipase C (PLC) inhibitor U‑73122, but not the inactive PLC inhibitor U‑73343. In the presence of a p42/p44 mitogen‑activated protein kinase (MAPK) inhibitor (PD98059), a p38 MAPK inhibitor (SB203580) or a c‑jun NH2‑terminal kinase (JNK) II inhibitor, CPE failed to induce membrane pacemaker depolarization. These results suggest that CPE may affect GI motility through modulating ICC pacemaker activity by activating the muscarinic M3 receptor and inducing the G‑protein dependent PLC and MAPK signaling pathways.

Modulating and opposite actions of two aqueous extracts prepared fromCinnamomum cassiaL. bark andQuercus ilexL. on the gastrointestinal tract in rats

“…53 Therefore, this effect of pacemaker potential depolarization might induce an intestinal-motility augmentation, as with various others medicinal plants including Liriope platyphylla 54 and Citrus unshiu. 55 Another possible mechanism could be the smooth muscle contractions which are known to depend on the intracellular calcium level. Because natural compounds caused an stimulation/inhibition of the contractions of the ileum, which involved an increase/decrease in cytosolic calcium, either by stimulating/inhibiting calcium inux or by releasing/ inhibiting calcium liberation from intracellular stores, or both.…”

Interstitial Cells of Cajal: Potential Targets for Functional Dyspepsia Treatment Using Medicinal Natural Products

“…ese results have been obtained mainly from cell-based experiments with ICCs using the patch-clamp technique. Many single-herb extracts [41,42], TCM drugs [14,26,[43][44][45][46][47][48][49][50][51], and herb-derived flavonoids [52] depolarize the pacemaker potential of ICCs in a dose-dependent manner. Depending on the herbal products, different receptors and their signaling pathways are involved in this depolarization process.…”

“…Molecular mechanism Depolarizers of the pacemaker potential of ICCs Gamisoyo-san [14], Citrus unshiu peel extracts [41], Dangkwisoo-san [43] Via M 3 receptor Magnolia officinalis [42] Via M 2 and M 3 receptors Banhasasim-tang [44] Via M 3 and 5-HT 3 receptors Daegeonjung-tang [45] Via M 3 and 5-HT 4 receptors Hesperidin, a citrus flavonoid [52] Via 5-HT 4 receptor Hwangryunhaedok-tang [46], Samhwangsasim-tang [47], Socheongryong-tang [48] Via 5-HT 3 and 5-HT 4 receptor Yukgunja-tang [49] Via ghrelin receptor Leejung-tang [90], Sengmek-san [50] Via PLC pathway Pyungwi-san [51] Via PKC pathway Inhibitors of the pacemaker potential of ICCs Galgeun-tang [26] Via α2-and β1-adrenoceptors Quercetin [91] Via opioid receptor signaling pathways M receptors: muscarinic acetylcholine receptors; 5-HT receptors: 5-hydroxytryptamine receptors; PLC: phospholipase C; PKC: protein kinase C. [53]. is decoction also promotes the numbers of stomach ICCs and the levels of SCF in diabetic rats [54].…”

Synthesis of MOFs/GO composite for corrosion resistance application on carbon steel

“…The equivalent circuit diagrams of the MOFs/GO and MOFs/ GR composite coatings are shown in Fig. 9(a) and (b), respectively, where R s is the solution resistance, the total polarization resistance R p (R p ¼ R s + R c + R ct ) represents the corrosion resistance of the coating to corrosive media, 55,56 R c is the coating resistance, R ct is charge transfer resistance, and CPE is the constant phase element; C coat and C dl are the capacitance response and charge transfer capacitance response of the double layer coating on the electrolyte/substrate interface, respectively. 57,58 Due to the unevenness and roughness of the coating surface, CPE is oen introduced instead of capacitor C, and its impedance is expressed by the following formula: 59…”