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| 1 | Oral treatment with plecanatide or dolcanatide attenuates visceral hypersensitivity via activation of guanylate cyclase-C in rat models显示文摘AIM To investigate the effects of plecanatide and dolcanatide on maintenance of paracellular permeability, integrity of tight junctions and on suppression of visceral hypersensitivity. METHODS Transport of fluorescein isothiocyanate(FITC)-dextran was measured to assess permeability across cell monolayers and rat colon tissues. Effects of plecanatide and dolcanatide on the integrity of tight junctions in Caco-2 and T84 monolayers and on the expression and localization of occludin and zonula occludens-1(ZO-1) were examined by immunofluorescence microscopy. Anti-nociceptive activity of these agonists was evaluated in trinitrobenzene sulfonic acid(TNBS)-induced inflammatory as well as in non-inflammatory partial restraint stress(PRS) rat models. Statistical significance between the treatment groups in the permeability studies were evaluated using unpaired t-tests.RESULTS Treatment of T84 and Caco-2 monolayers with lipopolysaccharide(LPS) rapidly increased permeability, which was effectively suppressed when monolayers were also treated with plecanatide or dolcanatide. Similarly, when T84 and Caco-2 monolayers were treated with LPS, cell surface localization of tight junction proteins occludin and ZO-1 was severely disrupted. When cell monolayers were treated with LPS in the presence of plecanatide or dolcanatide, occludin and ZO-1 were localized at the cell surface of adjoining cells, similar to that observed for vehicle treated cells. Treatment of cell monolayers with plecanatide or dolcanatide without LPS did not alter permeability, integrity of tight junctions and cell surface localization of either of the tight junction proteins. In rat visceral hypersensitivity models, both agonists suppressed the TNBS-induced increase in abdominal contractions in response to colorectal distension without affecting the colonic wall elasticity, and both agonists also reduced colonic hypersensitivity in the PRS model. CONCLUSION Our results suggest that activation of GC-C signaling might be involved in maintenance of barrier function, possibly through regulating normal localization of tight junction proteins. Consistent with these findings, plecanatide and dolcanatide showed potent antinociceptive activity in rat visceral hypersensitivity models. These results imply that activation of GC-C signaling may be an attractive therapeutic approach to treat functional constipation disorders and inflammatory gastrointestinal conditions. | Illona-Marie Boulete Anusha Thadi Catherine Beaufrand Viren Patwa Apoorva Joshi John A Foss E Priya Eddy Helene Eutamene Vaseem A Palejwala Vassilia Theodorou Kunwar Shailubhai | 2018 | World Journal of Gastroenterology2018，24，17： | 5 |
| 2 | The relations among environmental disclosure, environmental performance, and economic performance: a simultaneous equations approach显示文摘 | Sulaiman A Al-Tuwaijri Theodore E Christensen K.E Hughes | 2003 | Accounting, Organizations and Society2003，，5： | 2 |
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| 14 | Learning variable impedance control显示文摘 | Buchli J Stulp F Theodorou E | 2011 | International Journal of Robotics Re- search2011，30，7： | 1 |
| 15 | Effect of polystyrene on the morphology and physical properties of silicon carbide nanofibers 显示文摘 | BAHMAN E TAE W K MUHAMMAD S THEODORE T | 2009 | Materials Chemistry and Physics2009，118，1： | 1 |
| 16 | Railroad Costs,Returns to Scale and Excess 显示文摘 | Keeler Theodore E | 1974 | The Review of Economies and Statistics1974，2，56： | 1 |
| 17 | The Relationship between Board Structure and Firm Performance in the UK显示文摘 | Vafeas N Theodorou E | 1998 | British Accounting Review1998，30，： | 1 |
| 18 | The cost and risk impacts of rerouting railroad shipments of hazardous materials显示文摘 | Theodore S Glickman Erhan E | | 0，，02： | 1 |
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