Traditional Chinese formula, lubricating gut pill, stimulates cAMP-dependent CI(−) secretion across rat distal colonic mucosa.

Institute of Chinese Materia Medica, Shanghai University of TCM, Shanghai 201203, China.
Journal of ethnopharmacology (Impact Factor: 3). 12/2010; 134(2):406-13. DOI: 10.1016/j.jep.2010.12.031
Source: PubMed


Lubricating gut pill (LGP), a traditional Chinese formula, had been conformed to improve the loperamide-induced rat constipation by stimulation of Cl(-) secretion, but its mechanism has not been fully explored. Thus, the purpose of this study was to identify the action sites of LGP-stimulated Cl(-) secretion across rat distal colonic mucosa.
Rat distal colonic mucosa was mounted in Ussing chambers and short circuit current (I(SC)), apical Cl(-) current and basolateral K(+) current were recorded. Intracellular cyclic adenosine monophosphate (cAMP) content and protein kinase A (PKA) activity were determined with ELISA kit and the non-radioactive PepTag test, respectively.
LGP at 800μg/ml elicited a sustained increase in Cl(-) secretory response, which was inhibited by CFTR(inh)172, a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor. Permeabilizing apical membrane with nystatin revealed that LGP-stimulated basolateral K(+) current was significantly inhibited by KCNQ1 K(+) channel inhibitor chromanol 293B. LGP-stimulated I(SC) was markedly reduced by pretreatment with cis-N-[2-phenylcyclopentyl]-azacyclotridec-1-en-2amine (MDL-12,330A) and N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), but not with inhibitors of Ca(2+)-dependent signaling pathway. Treatment of tissue with LGP resulted in an increase in intracellular cAMP level and the activation in protein kinase A. The E-prostanoid(4) (EP)(4) receptor antagonist L-161,982 completely eliminated LGP-induced response.
The results showed that LGP enhances Cl(-) and fluid secretion via prostanoid receptor signaling and also cAMP and protein kinase A pathway, subsequently triggering the activation of apical Cl(-) channels mostly CFTR and basolateral cAMP-dependent K(+) channel.

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    • "In constipation, marked decreases in fecal discharge and delayed fecal pellet transit in the large intestinal lumen caused by absorption of water into the fecal pellets are observed; accordingly, the water content of the discharged fecal pellets is decreased markedly. Therefore, these changes in fecal parameters, including discharged fecal pellet number and water content, have been used as indices of the effects of various laxative agents [37, 41]. The increases in discharged fecal pellet number and water content in the constipated rats induced by treatment with either FRe dosage, the liquid yoghurt single formula, or the three BFRe concentrations were considered direct evidence of the beneficial laxative effects of these agents. "
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