Isothiocyanate inhibits restitution and wound repair after injury in the stomach: Ex vivo and in vitro studies

Regina Ragasa, Eiji Nakamura, Lisa Marrone, Saeko Yanaka, Shusaku Hayashi, Koji Takeuchi, Susan J. Hagen

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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 (H 2DIDS) (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 μM, 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.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume323
Issue number1
DOIs
Publication statusPublished - Oct 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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