title: Emodin induces chloride secretion in rat distal colon through activation of mast cells and enteric neurons.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The results suggest that emodin-induced colonic Cl(-) secretion involves mast cell degranulation and activation of cholinergic and non-cholinergic submucosal neurons.
authors: Department of Physiology and Pathophysiology, School of Basic Medical Science, Institute of Pharmacology, Xuanwu Hospital, Capital Medical University, Beijing, China.
authors: J-D
authors: JD
authors: Xu
authors: S
authors: S
authors: Liu
authors: W
authors: W
authors: Wang
authors: L-S
authors: LS
authors: Li
authors: X-F
authors: XF
authors: Li
authors: Y
authors: Y
authors: Li
authors: H
authors: H
authors: Guo
authors: T
authors: T
authors: Ji
authors: X-Y
authors: XY
authors: Feng
authors: X-L
authors: XL
authors: Hou
authors: Y
authors: Y
authors: Zhang
authors: J-X
authors: JX
authors: Zhu
mesh_terms: D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism*; D004642:Emodin / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology
chemical_list: D002712:Chlorides; D007004:Hypoglycemic Agents; D049994:Sodium Potassium Chloride Symporter Inhibitors; D002034:Bumetanide; D006632:Histamine; D004642:Emodin; D005905:Glyburide