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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Bao, Hui Fang Liu, Lian Self, Julie Duke, Billie Jeanne Ueno, Ryuji Eaton, Douglas C. |
| Description | Country affiliation: United States Author Affiliation: Bao HF ( Emory Univ. School of Medicine, Dept. of Physiology, Whitehead Biomedical Research Bldg., 615 Michael St., Atlanta, GA 30322, USA.) |
| Abstract | The bicyclic fatty acid lubiprostone (formerly known as SPI-0211) activates two types of anion channels in A6 cells. Both channel types are rarely, if ever, observed in untreated cells. The first channel type was activated at low concentrations of lubiprostone (<100 nM) in >80% of cell-attached patches and had a unit conductance of ∼3–4 pS. The second channel type required higher concentrations (>100 nM) of lubiprostone to activate, was observed in ∼30% of patches, and had a unit conductance of 8–9 pS. The properties of the first type of channel were consistent with ClC-2 and the second with CFTR. ClC-2's unit current strongly inwardly rectified that could be best fit by models of the channel with multiple energy barrier and multiple anion binding sites in the conductance pore. The open probability and mean open time of ClC-2 was voltage dependent, decreasing dramatically as the patches were depolarized. The order of anion selectivity for ClC-2 was Cl > Br > $NO_{3}$ > I > SCN, where SCN is thiocyanate. ClC-2 was a “double-barreled” channel favoring even numbers of levels over odd numbers as if the channel protein had two conductance pathways that opened independently of one another. The channel could be, at least, partially blocked by glibenclamide. The properties of the channel in A6 cells were indistinguishable from ClC-2 channels stably transfected in HEK293 cells. CFTR in the patches had a selectivity of Cl > Br ≫ $NO_{3}$ ≅ SCN ≅ I. It outwardly rectified as expected for a single-site anion channel. Because of its properties, ClC-2 is uniquely suitable to promote anion secretion with little anion reabsorption. CFTR, on the other hand, could promote either reabsorption or secretion depending on the anion driving forces. |
| File Format | HTM / HTML |
| ISSN | 01931857 |
| e-ISSN | 15221547 |
| DOI | 10.1152/ajpgi.00366.2007 |
| Journal | AJP: Gastrointestinal and Liver Physiology |
| Issue Number | 2 |
| Volume Number | 295 |
| Language | English |
| Publisher | American Physiological Society |
| Publisher Date | 2008-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Physiology Discipline Gastroenterology Alprostadil Analogs & Derivatives Chloride Channels Physiology Cystic Fibrosis Transmembrane Conductance Regulator Epithelial Cells Drug Effects Administration & Dosage Pharmacology Animals Cells, Cultured Glyburide Iodides Lubiprostone Patch-clamp Techniques Thiocyanates Xenopus Laevis Comparative Study Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Hepatology Physiology Physiology (medical) Gastroenterology |
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