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1、DrugDesign,DevelopmentandTherapyDovepressopenaccesstoscientificandmedicalresearchOpenAccessFullTextArticleREviEwPharmacologyandclinicalpotentialofguanylylcyclaseCagonistsinthetreatmentofulcerativecolitisGiovanniMPitariAbstract:Agonistsofthetransmembraneintestinalreceptorg
2、uanylylcyclaseC(GCC)haverecentlyattractedinterestaspromisinghumantherapeutics.PeptideligandsthatcanspecificallyDepartmentofPharmacologyandExperimentalTherapeutics,induceGCCsignalingintheintestineincludeendogenoushormonesguanylinanduroguanylin,ThomasJeffersonUniversity,dia
3、rrheagenicbacterialenterotoxins(ST),andsyntheticdrugslinaclotide,plecanatide,andPhiladelphia,PA,USASP-333.TheseagonistsbindtoGCCatintestinalepithelialsurfacesandactivatethereceptor’sintracellularcatalyticdomain,aneventinitiatingdiscretebiologicalresponsesuponconversionofg
4、uanosine-5′-triphosphatetocyclicguanosinemonophosphate.AprincipalactionofGCCagonistsinthecolonisthepromotionofmucosalhomeostasisanditsdependentbarrierfunc-tion.Herein,GCCagonistsarebeingdevelopedasnewmedicationstotreatinflammatorybowelForpersonaluseonly.diseases,pathologi
5、calconditionscharacterizedbymucosalbarrierhyperpermeability,abnormalimmunereactions,andchroniclocalinflammation.ThisreviewwillpresentimportantconceptsunderlyingthepharmacologyandtherapeuticutilityofGCCagonistsforpatientswithulcerativecolitis,oneofthemostprevalentinflammat
6、oryboweldiseasedisorders.Keywords:inflammatoryboweldisease,GCCagonists,cyclicGMPIntroductionVideoabstractUlcerativecolitis(UC)isamajorclinicalsyndromeofinflammatoryboweldiseases(IBDs)andischaracterizedbychronicmucosalinflammationofthecolon.Recurrentbloodydiarrhea,tenesmus
7、andrectalurgencyarethemostcommonsymptomsforUC,butextraintestinalmanifestationsmayalsooccur.1DiagnosisofUCismainlybasedonintestinalmucosaexaminationandtissuehistopathologyfollowingcolonoscopyDrugDesign,DevelopmentandTherapydownloadedfromhttps://www.dovepress.com/by117.165.
8、40.65on24-Jul-2018andbiopsy.1TheworldwideannualincidenceofUCis0.5–25per100,000persons,withthehig
