Department of Physiology and Pathophysiology, School of Basic Medical Science, Institute of Pharmacology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Br J Pharmacol. 2012 Jan;165(1):197-207. doi: 10.1111/j.1476-5381.2011.01573.x.
Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an active component of many herb-based laxatives. However, its mechanism of action is unclear. The aim of the present study was to investigate the role of mast cells and enteric neurons in emodin-induced ion secretion in the rat colon.
Short-circuit current (I(SC)) recording was used to measure epithelial ion transport. A scanning ion-selective electrode technique was used to directly measure Cl(-) flux (J(Cl)-) across the epithelium. RIA was used to measure emodin-induced histamine release.
Basolateral addition of emodin induced a concentration-dependent increase in I(SC) in colonic mucosa/submucosa preparations, EC(50) 75 µM. The effect of emodin was blocked by apically applied glibenclamide, a Cl(-) channel blocker, and by basolateral application of bumetanide, an inhibitor of the Na(+) -K(+) -2Cl(-) cotransporter. Emodin-evoked J(Cl)- in mucosa/submucosa preparations was measured by scanning ion-selective electrode technique, which correlated to the increase in I(SC) and was significantly suppressed by glibenclamide and bumetanide. Pretreatment with tetrodotoxin and the muscarinic receptor antagonist atropine had no effect on emodin-induced ΔI(SC) in mucosa-only preparations, but significantly reduced emodin-induced ΔI(SC) and J(Cl)- in mucosa/submucosa preparations. The COX inhibitor indomethacin, the mast cell stabilizer ketotifen and H(1) receptor antagonist pyrilamine significantly reduced emodin-induced ΔI(SC) in mucosa and mucosa/submucosa preparations. The H(2) receptor antagonist cimetidine inhibited emodin-induced ΔI(SC) and J(Cl)- only in the mucosa/submucosa preparations. Furthermore, emodin increased histamine release from the colonic mucosa/submucosa tissues.
The results suggest that emodin-induced colonic Cl(-) secretion involves mast cell degranulation and activation of cholinergic and non-cholinergic submucosal neurons.
大黄素（1,3,8-三羟基-6-甲基蒽醌）是许多草药泻药的有效成分。然而，其作用机制尚不清楚。本研究旨在探讨肥大细胞和肠神经元在大黄素诱导的大鼠结肠离子分泌中的作用。
采用短路电流（Isc）记录法测量上皮离子转运。采用扫描离子选择性电极技术直接测量上皮跨膜 Cl(-)流（J(Cl)-）。放射免疫分析法（RIA）用于测量大黄素诱导的组胺释放。
基底外侧加入大黄素可诱导结肠黏膜/黏膜下层组织中 Isc 浓度依赖性增加，EC50 为 75µM。大黄素的作用被上皮侧应用的格列本脲（Cl(-)通道阻滞剂）和基底外侧应用的布美他尼（Na(+) -K(+) -2Cl(-)共转运体抑制剂）所阻断。通过扫描离子选择性电极技术测量大黄素诱导的 J(Cl)-在黏膜/黏膜下层组织中，其与 Isc 的增加相关，并被格列本脲和布美他尼显著抑制。在仅有黏膜的制剂中，预先给予河豚毒素和毒蕈碱受体拮抗剂阿托品对大黄素诱导的ΔI(SC)没有影响，但在黏膜/黏膜下层制剂中显著降低了大黄素诱导的ΔI(SC)和 J(Cl)-。COX 抑制剂吲哚美辛、肥大细胞稳定剂酮替芬和 H1 受体拮抗剂苯海拉明显著降低了黏膜和黏膜下层制剂中大黄素诱导的ΔI(SC)。H2 受体拮抗剂西咪替丁仅抑制黏膜/黏膜下层制剂中大黄素诱导的ΔI(SC)和 J(Cl)-。此外，大黄素增加了结肠黏膜/黏膜下层组织中组胺的释放。
结果表明，大黄素诱导的结肠 Cl(-)分泌涉及肥大细胞脱颗粒和激活胆碱能和非胆碱能黏膜下神经元。
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