Traditional Chinese formula, lubricating gut pill, improves loperamide-induced rat constipation involved in enhance of Cl- secretion across distal colonic epithelium.
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.
Wu
Dazheng
D
Institute of Chinese Materia Medica, Shanghai University of TCM, Shanghai, China.
Wang
Xinhong
X
Zhou
Jiyan
J
Yuan
Jianye
J
Cui
Bo
B
An
Rui
R
Hu
Zhibi
Z
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
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