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1、PhysiolRev93:405480,2013doi:10.1152/physrev.00001.2012RELAXINFAMILYPEPTIDESANDTHEIRRECEPTORSR.A.D.Bathgate,M.L.Halls,E.T.vanderWesthuizen,G.E.Callander,M.Kocan,andR.J.SummersDrugDiscoveryBiology,MonashInstituteofPharmaceuticalSciences&DepartmentofPharmacology,MonashUniversity,Victoria,Australia;Flor
2、eyNeurosciencesInstitutesandDepartmentofBiochemistryandMolecularBiology,TheUniversityofMelbourne,Victoria,Australia;andUniversitédeMontréal,InstitutdeRechercheenImmunologieetCancérologie,PharmacologieMoléculaire,Montréal,CanadaBathgateRAD,HallsML,vanderWesthuizenET,CallanderGE,KocanM,SummersRJ.Relax
3、inFamilyPeptidesandTheirReceptors.PhysiolRev93:405480,2013;doi:10.1152/physrev.00001.2012.TherearesevenrelaxinfamilyLpeptidesthatareallstructurallyrelatedtoinsulin.Relaxinhasmanyrolesinfemaleandmalereproduction,asaneuropeptideinthecentralnervoussystem,asavasodilatorandcardiacstimulantinthecardiovasc
4、ularsystem,andasanantifibroticagent.Insulin-likepeptide-3(INSL3)hasclearlydefinedspecialistrolesinmaleandfemalereproduc-tion,relaxin-3isprimarilyaneuropeptideinvolvedinstressandmetaboliccontrol,andINSL5iswidelydistributedparticularlyinthegastrointestinaltract.Althoughtheyarestructurallyrelatedtoinsuli
5、n,therelaxinfamilypeptidesproducetheirphysiologicaleffectsbyactivatingagroupoffourGprotein-coupledreceptors(GPCRs),relaxinfamilypeptidereceptors14(RXFP14).RelaxinandINSL3arethecognateligandsforRXFP1andRXFP2,respectively,thatareleucine-richrepeatcontainingGPCRs.RXFP1activatesawidespectrumofsignalingp
6、athwaystogeneratesecondmessengersthatincludecAMPandnitricoxide,whereasRXFP2activatesasubsetofthesepathways.Relaxin-3andINSL5arethecognateligandsforRXFP3andRXFP4thatarecloselyrelatedtosmallpeptidereceptorsthatwhenactivatedinhibitcAMPproductionandactivateMAPkinases.Althoughtherearestillmanyunansweredq
7、uestionsregardingthemodeofactionofrelaxinfamilypeptides,itisclearthattheyhaveimportantphysiologicalrolesthatcouldbeexploitedfortherapeuticbenefit.I.INTRODUCTION:THEDISCOVERYOF...405turition.In1926hesho
