Emodin induces chloride secretion in rat distal colon through activation of mast cells and enteric neurons

BACKGROUND AND PURPOSE 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.

EXPERIMENTAL APPROACH 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.

KEY RESULTS Basolateral addition of emodin induced a concentration‐dependent increase in I_SC in colonic mucosa/submucosa preparations, EC₅₀ 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 H₁ receptor antagonist pyrilamine significantly reduced emodin‐induced ΔI_SC in mucosa and mucosa/submucosa preparations. The H₂ 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.

CONCLUSIONS AND IMPLICATIONS The results suggest that emodin‐induced colonic Cl^‐ secretion involves mast cell degranulation and activation of cholinergic and non‐cholinergic submucosal neurons.

DOI: 10.1111/j.1476-5381.2011.01573.x

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