ScientificBackground: | OX2RisoneoftworeceptorsthatrecognizethepeptideneurotransmittersorexinAandorexinB1.OrexinAandBare33and28aminoacidsinlength,respectively,andarederivedfromacommonprecursor,prepro-orexin.OX1RbindsorexinAwithten-foldgreateraffinitythantoorexinB.OX2Rbindsbothligandswithsimilaraffinities2,3.BothOX1RandOX2Rbelongtothe7-transmembranedomain,Gprotein-coupledreceptor(GPCR)superfamily.OX2RisthoughttotransmitsignalsthroughtheGa11classofGproteins,resultingintheactivationofphospholipaseCwithsubsequenttriggeringofthephosphatidylinositolcascadeandaninfluxofextracellularCa2+,probablythroughtransientreceptorpotential(TRP)channels2,3.TheorexinsystemhasbeenshowntobeinvolvedintheregulationofsleepandwakefulnessstatesandOX1RknockoutmiceshowdefectsintheregulationofREMsleep,amongotherphenotypicalterations4.Inaddition,theorexinsystemisinvolvedinregulatingautonomicfunctionssuchasbloodpressureandheartrate,aswellasinmechanismsthatregulatetherewardresponseinthebrain4.OX2Risexpressedinboththecentralnervoussystemandperipherallocationssuchasgastrointestinaltissues,pancreas,andtestis.2. |