title: Traditional Chinese formula, lubricating gut pill, improves loperamide-induced rat constipation involved in enhance of Cl- secretion across distal colonic epithelium.
abstract: OBJECTIVE
  Lubricating gut pill (LGP), a traditional Chinese formula, was widely used for the treatment of chronic constipation, especially in the elderly, in China. However, it is unclear whether LGP-induced laxative and/or lubricating effect is involved in water and electrolytes transport in distal colonic epithelium.
  
  
  METHODS
  The present study was designed to evaluate the effect of LGP on Cl(-) secretion across rat distal colonic epithelium mounted in Ussing chambers, and on a rat constipation model induced by loperamide, respectively.
  
  
  RESULTS
  Application of LGP in the apical side elicited a sustained increase in short circuit current (I(SC)) response in a concentration-dependent manner. Evidence that LGP-stimulated I(SC) was due to Cl(-) secretion is based on inhibition of current by (a) a Na(+)-K(+)-2Cl(-) cotransporter inhibitor bumetanide, (b) removal of Cl(-) ions in bath solution, and (c) the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel blocker DPC, suggesting that a apical cAMP-dependent Cl(-) channel was activated. LGP-stimulated I(SC) was also strongly inhibited by pretreatment with clotrimazole, indicating that the basolateral K(+) channel was also involved in maintaining this cAMP-dependent Cl(-) secretion. Pretreatment of tissues with indomethacin, but not atropine, tetrodotoxin or hexamethonium, inhibited LGP-induced response. In a rat constipation model, oral administration with LGP was significantly restored number of fecal pellets, water content and mucus secretion compared with loperamide-treated group alone.
  
  
  CONCLUSIONS
  LGP enhances Cl(-) secretion that is mostly mediated through the release of cyclooxygenase metabolites, by which provided an osmotic force for the subsequent laxative action observed in the rat constipation model.
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of TCM, Shanghai, China.
authors.forename: Dazheng
authors.initials: D
authors.lastname: Wu
authors.forename: Xinhong
authors.initials: X
authors.lastname: Wang
authors.forename: Jiyan
authors.initials: J
authors.lastname: Zhou
authors.forename: Jianye
authors.initials: J
authors.lastname: Yuan
authors.forename: Bo
authors.initials: B
authors.lastname: Cui
authors.forename: Rui
authors.initials: R
authors.lastname: An
authors.forename: Zhibi
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D003248:Constipation / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D000242:Cyclic AMP / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors / Q000378:metabolism; D003672:Defecation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D007419:Intestinal Secretions / Q000378:metabolism*; D054368:Laxatives / Q000494:pharmacology*; D008139:Loperamide; D008297:Male; D008516:Medicine, Chinese Traditional; D008564:Membrane Potentials; D009995:Osmosis; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology
chemical_list: D002712:Chlorides; D018680:Cholinergic Antagonists; D016861:Cyclooxygenase Inhibitors; D004365:Drugs, Chinese Herbal; D054368:Laxatives; D026902:Potassium Channel Blockers; D049994:Sodium Potassium Chloride Symporter Inhibitors; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D008139:Loperamide; D000242:Cyclic AMP; D011451:Prostaglandin-Endoperoxide Synthases