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Traditional Chinese formula, lubricating gut pill, stimulates cAMP-dependent Cl− secretion across rat distal colonic mucosa
- Source :
-
Journal of Ethnopharmacology . Mar2011, Vol. 134 Issue 2, p406-413. 8p. - Publication Year :
- 2011
-
Abstract
- Abstract: Aim of the study: 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. Materials and methods: 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. Results: LGP at 800μg/ml elicited a sustained increase in Cl− secretory response, which was inhibited by CFTRinh172, 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 Ca2+-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-prostanoid4 (EP)4 receptor antagonist L-161,982 completely eliminated LGP-induced response. Conclusions: 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. [Copyright &y& Elsevier]
- Subjects :
- *ALTERNATIVE medicine
*ANALYSIS of variance
*ANIMAL experimentation
*BIOLOGICAL models
*CHLORIDES
*COMPUTER software
*ELECTROPHYSIOLOGY
*ENZYME-linked immunosorbent assay
*INTESTINAL mucosa
*MEDICINAL plants
*BOTANIC medicine
*CHINESE medicine
*METABOLISM
*RATS
*RESEARCH funding
*T-test (Statistics)
*DATA analysis
Subjects
Details
- Language :
- English
- ISSN :
- 03788741
- Volume :
- 134
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Ethnopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 59326590
- Full Text :
- https://doi.org/10.1016/j.jep.2010.12.031