Angiotensin-2-Mediated Ca2+ Signaling in the Retinal Pigment Epithelium Role of Angiotensin-Receptor- Associated-Protein and TRPV2 Channel 英文参考文献.docVIP
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Angiotensin-2-MediatedCa2SignalingintheRetinalPigmentEpitheliumRoleofAngiotensin-Receptor-Associated-ProteinandTRPV2Channel英文参考文献
Angiotensin-2-MediatedCa2+SignalingintheRetinal
PigmentEpithelium:RoleofAngiotensin-Receptor-
Associated-ProteinandTRPV2Channel
ReneBarro-Soria1¤,JuliaStindl1,ClaudiaMu¨ller1,RenateFoeckler1,VladimirTodorov2,3,HayoCastrop2,
OlafStrau?1*
1Experimental Ophthalmology, Eye Hospital, University Medical Center Regensburg, Regensburg, Germany, 2Institute of Physiology, University of Regensburg,
Regensburg,Germany,3LaboratoryforExperimentalNephrology,DresdenUniversityofTechnology,Dresden,Germany
Abstract
Angiotensin II (AngII) receptor (ATR) is involved in pathologic local events such as neovascularisation and inflammation
includinginthebrainandretina.Theretinalpigmentepithelium(RPE)expressesATRinitsAT1Rform,angiotensin-receptor-
associated protein (Atrap), and transient-receptor-potential channel-V2 (TRPV2). AT1R and Atrap co-localize to the
basolateralmembraneoftheRPE,asshownbyimmunostaining.StimulationofporcineRPE(pRPE)cellsbyAngIIresultsin
2+
biphasicincreasesinintracellularfreeCa inhibitedbylosartan.XestosponginC(xestC)andU-73122,blockersofIP3Rand
2+
2+
PLCrespectively,reducedAngII-evokedCa response.RPEcellsfromAtrap2/2miceshowedsmallerAngII-evokedCa peak
2+
(by22%)andlossofsustainedCa elevationcomparedtowild-type.TheTRPVchannelactivatorcannabidiol(CBD)at15mM
stimulatesintracellularCa -risesuggestingthatporcineRPEcellsexpressTRPV2channels.Furtherevidencesupportingthe
2+
functionalexpressionofTRPV2channelscomesfromexperimentsin which100 mMSKF96365 (aTRPVchannel inhibitor)
reducedthecannabidiol-inducedCa -rise.ApplicationofSKF96365orreductionofTRPV2expressionbysiRNAreducedthe
2+
2+
sustainedphaseofAngII-mediatedCa transientsby53%.ThussystemicAngII,aneffectorofthelocalrenin-angiotensin
systemstimulatesbiphasicCa transientsintheRPEbyreleasingCa fromcytosolicIP3-dependentstoresandactivating
ATR/AtrapandTRPV2channelstogenerateasustainedCa elevation.
2+
2+
2+
Citation:Barro-SoriaR,StindlJ,Mu¨llerC,FoecklerR,TodorovV,etal.(2012)Angiotensin-2-
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