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| Content Provider | Springer Nature Link |
|---|---|
| Author | Wongsamitkul, Nisa Sirianant, Lalida Muanprasat, Chatchai Chatsudthipong, Varanuj |
| Copyright Year | 2009 |
| Abstract | The present study examined the effects and mechanisms of actions of penta-m-digalloyl-glucose (PDG), a hydrolysable tannin extracted from Chinese gallnut, on cystic fibrosis transmembrane conductance regulator protein (CFTR).Fisher rat thyroid cells stably expressing human CFTR (FRT cells) and human intestinal T84 cells were used as cell models to investigate the effects of PDG on chloride secretion using short-circuit current analysis. The mechanisms by which PDG affected chloride secretion were also examined. Finally, in vivo antidiarrheal efficacy and effects of PDG on intestinal fluid absorption were evaluated in mouse closed-loop models.In FRT cells, apical chloride current induced by forskolin, CPT-cAMP and apigenin were reversibly inhibited by PDG (IC50 ∼ 10 µM) without effects on intracellular cAMP content and cell viability. Similarly, in T84 cells, PDG effectively inhibited chloride secretion induced by forskolin and cholera toxin. However, it had no effect on calcium-induced chloride secretion. In mice, a single intraluminal injection of PDG (0.6 mg/kg) reduced cholera toxin-induced intestinal fluid secretion by 75% with no effect on intestinal fluid absorption.PDG represents a new class of CFTR inhibitors. Further development of this class of compounds may provide a new therapeutic intervention for diarrhea. |
| Starting Page | 490 |
| Ending Page | 497 |
| Page Count | 8 |
| File Format | |
| ISSN | 07248741 |
| Journal | Pharmaceutical Research |
| Volume Number | 27 |
| Issue Number | 3 |
| e-ISSN | 1573904X |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2010-01-07 |
| Publisher Place | Boston |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | CFTR chloride secretion diarrhea tannin Biomedical Engineering Medical Law Biochemistry Pharmacy Pharmacology/Toxicology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science |
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