Biogenic amines activate blood leukocytes via trace amine‐associated receptors TAAR1 and TAAR2

[摘要] Certainbiogenicamines,suchas2‐PEA,TYR,orT1AM,modulatebloodpressure,cardiacfunction,brainmonoaminergicsystems,andolfaction‐guidedbehaviorbyspecificallyinteractingwithmembersofagroupofrhodopsin‐likereceptors,TAAR.Areceptorthatisabsentfromolfactoryepitheliabuthadlongbeenidentifiedinthebrainandavarietyofperipheraltissues,TAAR1hasbeenfoundrecentlyinbloodBcells,suggestingafunctionalroleofTAAR1inthesecells.Withthepresentstudy,wehavesetouttoclarifytheexpressionandfunctionalrolesofTAARindifferentisolatedhumanbloodleukocytetypes.Here,wereportthefunctionalexpressionofTAAR1anditsclosestrelativeTAAR2inbloodPMNandTandBcells.BothreceptorsarecoexpressedinasubpopulationofPMN,wheretheyarenecessaryforthechemosensorymigrationtowardtheTAAR1ligands2‐PEA,TYR,andT1AM,withEC50valuesof0.43±0.05nM,0.52±0.05nM,and0.25±0.04nM,respectively.Thesameamines,withsimilarpotencies,triggeredcytokineorIgsecretion,inpurifiedbloodTorBcells,respectively.Notably,2‐PEAregulatedmRNAexpressionof28Tcellfunction‐relatedgenes,abovealloftheCCL5.InsiRNA‐guidedexperiments,TAAR1andTAAR2provedtobenecessaryforamine‐inducedbloodleukocytefunctions.Insummary,ourresultsdemonstratethatbiogenicaminespotentlyregulatebloodcellfunctionsviaTAAR1andTAAR2andopentheperspectiveoftheirspecificpharmacologicalmodulation...

[学科分类] 生理学

[关键词] Olfactory receptors;GPCR;dimers;siRNA;cytokines;immune response