Traditional Chinese formula, lubricating gut pill, improves loperamide-induced rat constipation involved in enhance of Cl− secretion across distal colonic epithelium

Aim of the study: 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. Materials and 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. [Copyright &y& Elsevier]