論文 - 詳細
| RRC ID | 43028 |
|---|---|
| 著者 | Ragasa R, Nakamura E, Marrone L, Yanaka S, Hayashi S, Takeuchi K, Hagen SJ. |
| タイトル | Isothiocyanate inhibits restitution and wound repair after injury in the stomach: ex vivo and in vitro studies. |
| ジャーナル | J Pharmacol Exp Ther |
| Abstract |
The role of isothiocyanate (ITC) in blocking epithelial restitution after injury and in the recovery of round wounds was examined in the ex vivo guinea pig stomach and in rat gastric mucosal-1 (RGM1) cells, respectively. For this, recovery of transepithelial electrical resistance and morphology after injury or the closure of round wounds was evaluated in the presence of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) or 4,4-diisothiocyanatodihydrostilbene-2,2'-disulfonic acid (H2DIDS) (two ITC groups), 4-acetamido-4-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) (one ITC group), or 4,4-diinitrostilbene-2,2'-disulfonic acid (DNDS) (no ITC groups). Wounded RGM1 cells were also incubated with bicarbonate-free buffer, ATP, barium, or phloretin to determine the mechanism of ITC inhibition. At 300 microM, DIDS or H2DIDS blocked restitution and wound repair by 100%, SITS blocked wound repair by 50%, and DNDS blocked wound repair by 2%. These results demonstrate the dependence of restitution and wound repair on ITC. ITC-binding purino (ATP) receptors and KATP channels were investigated as potential sites of inhibition, but they were found not to be the target of ITC in wound repair. Phloretin, blocking the monocarboxylate transporter (MCT), dose-dependently inhibited wound repair, and this result was exacerbated when the sodium bicarbonate cotransporter (NBC) was also blocked by bicarbonate-free conditions, resulting in 100% inhibition of wound repair with no reduction in viability when both transporters were blocked simultaneously. ITC potently inhibits both MCT and NBC, which may account for the inhibitory action of DIDS during restitution and wound repair. Reverse transcription-polymerase chain reaction data verified that MCT-1 is expressed in RGM1 cells. In conclusion, our results suggest that bicarbonate and monocarboxylate transport may work cooperatively to facilitate restitution of the gastric mucosa after injury. |
| 巻・号 | 323(1) |
| ページ | 1-9 |
| 公開日 | 2007-10-1 |
| DOI | 10.1124/jpet.107.121640 |
| PII | jpet.107.121640 |
| PMID | 17609422 |
| MeSH | Animals Cell Line Cell Survival / drug effects Dose-Response Relationship, Drug Epithelial Cells / drug effects* Epithelial Cells / pathology Gastric Mucosa* / drug effects Gastric Mucosa* / injuries Gastric Mucosa* / metabolism Gastric Mucosa* / pathology Guinea Pigs Isocyanates / toxicity* KATP Channels Male Monocarboxylic Acid Transporters / physiology Potassium Channels, Inwardly Rectifying / physiology Rats Receptors, Purinergic / physiology Sodium-Bicarbonate Symporters / physiology Wound Healing / drug effects* |
| IF | 3.561 |
| 引用数 | 5 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | |