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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 | Evapotranspiration components determined by stable isotope, sap flow and eddy covariance techniques显示文摘 | D.G. Williams W. Cable K. Hultine J.C.B. Hoedjes E.A. Yepez V. Simonneaux S. Er-Raki G. Boulet H.A.R. de Bruin A. Chehbouni O.K. Hartogensis F. Timouk | 2004 | Agricultural and Forest Meteorology2004，，3： | 2 |
| 3 | Assessing the written communication skills of medical school graduates 显示文摘 | Boulet JR Rebbecchi TA Denton EC | 2004 | Adv Health Sci Educ Theory Pract2004，9，1： | 1 |
| 4 | Breast cancer molecularsub- classification and estrogen receptor expression to predict efficacyof adju- vant anthracycllnes-based chemotherapy: abiomarker study from two ran- domized trials显示文摘 | Conforti R Boulet T Tomasic G | 2007 | Ann Oncol2007，18，9： | 1 |
| 5 | Roflumilast attenuates allergen-induced inflammation in mild asthmatic subjects显示文摘 | Gauvreau GM Boulet LP Schmid-Wirlitsch C | 2011 | Respir Res2011，12，： | 1 |
| 6 | Multiple roles of Hoxal 1 and Hoxdl 1 in the formation of the mammalian forelimb zeugopod 显示文摘 | Boulet AM Capecchi MR | 2004 | Development2004，131，2： | 1 |
| 7 | Structural changes in airway diseasescharacteristics,mechanisms,consequences and pharmacologicmodulation显示文摘 | Bergeron C Boulet L P | 2006 | Chest2006，129，4： | 1 |
| 8 | A randomized study comparing ciclesonide and fluticasone propionate in patients with moderate persistent asthma显示文摘 | Boulet LP Bateman ED Voves R | 2007 | Respir Med2007，101，8： | 1 |
| 9 | Development and pharmacological characterization of a rat model of osteoarthritis pain 显示文摘 | Pomonis JD Boulet JM Gottshall SL | 2005 | Pain2005，114，3： | 1 |
| 10 | State of the art in standardized patient programs : A survey of osteopathic medical schools 显示文摘 | Errich ettiAM Gimpel J R Boulet JR | 2002 | Medical Education2002，102，11： | 1 |
| 11 | The CONCEPT trial:A1-year,multicenter,randomized,double-blind,double-dummy comparison of a stable dosing regimen of salmeterol/fluticasone propionate with an adjustable maintenance dosing regimen of formoterol/budesonide in adults with persistent asthma显示文摘 | Fitz Gerald JM Boulet LP Follows RM | 2005 | Clin Ther2005，27，： | 1 |
| 12 | Quality assur-ance methods for performance-based assessments显示文摘 | Boulet JR McKinley DW Whelan GP | 2003 | AdvHealth Sci Educ Theory Pract2003，8，1： | 1 |
| 13 | Structural changes in airway diseases: characteristics, mechanisms, consequences, and pharmacologic modulation 显示文摘 | Bergeron C Boulet LP | 2006 | Chest2006，129，4： | 1 |
| 14 | Hantan papillomavirus 16 load and E2/E6 ratio in HPV16-positive women: biomarkers for cervical intraepithelial neoplasia > or = 2 in a liquid-based cytology setting? 显示文摘 | Boulet G A Benoy I H Depuydt C E | 2009 | Cancer Epidemiol Biomarkers Prev2009，18，11： | 1 |
| 15 | Effects of an Anti-TSLP Antibody on AllergenInduced Asthmatic Responses显示文摘 | GAUVREAU G M O′BYRNE P M BOULET L P | 2014 | N Engl J Med2014，370，： | 1 |
| 16 | Relationship between atherosclerosis and the sleep apnea syndrome: an intravascular ultrasound study 显示文摘 | TURMEL J SIRIIS F BOULET L P | 2009 | Int J Cardiol2009，132，2： | 1 |
| 17 | Structural changes in airway diseases:characteristics,mechanisms,consequences,and pharmacologic modulation显示文摘 | Bergeron C Boulet LP | 2006 | Chest2006，129，4： | 1 |
| 18 | Odd sound processing in the sleeping brain显示文摘 | Ruby P Caclin A Boulet S | 2008 | J Cogn Neurosci2008，20，： | 1 |
| 19 | Comparison of techniques for detection of discontinuities in temperature series 显示文摘 | Ducre-Robitaille J C Vincent L A Boulet G | 2003 | International Journal of Climatology2003，23，： | 1 |
| 20 | Smoking and asthma: clinical and radiologic features, lung function, and airway inflamamtion 显示文摘 | Boulet LP Lemiere C Archambault F | 2006 | Chest2006，129，3： | 1 |
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