Presynaptic Nicotinic α7 and Non-α7 Receptors Stimulate Endogenous GABA Release from Rat Hippocampal Synaptosomes through Two Mechanisms of Action 英文参考文献.docVIP

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Presynaptic Nicotinic α7 and Non-α7 Receptors Stimulate Endogenous GABA Release from Rat Hippocampal Synaptosomes through Two Mechanisms of Action 英文参考文献.doc

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Presynaptic Nicotinic α7 and Non-α7 Receptors Stimulate Endogenous GABA Release from Rat Hippocampal Synaptosomes through Two Mechanisms of Action 英文参考文献

PresynapticNicotinica7andNon-a7ReceptorsStimulate EndogenousGABAReleasefromRatHippocampal SynaptosomesthroughTwoMechanismsofAction StefaniaZappettini1,MassimoGrilli1,FedericaLagomarsino1,AnnaCavallero1,ErnestoFedele1,2 ,Mario Marchi1,2,3 * 1Section of Pharmacology and Toxicology, Department of Experimental Medicine, University of Genoa, Genoa, Italy, 2Center of Excellence for Biomedical Research, UniversityofGenoa,Genoa,Italy,3NationalInstituteofNeuroscience,Genoa,Italy Abstract Background:Althoughconvergingevidencehassuggestedthatnicotinicacetylcholinereceptors(nAChR)playaroleinthe modulationofGABAreleaseinrathippocampus,thespecificinvolvementofdifferentnAChRsubtypesatpresynapticlevel isstillamatterofdebate.Inthepresentworkweinvestigated,usingselectivea7anda4b2nAChRagonists,thepresenceof differentnAChRsubtypesonhippocampalGABAnerveendingstoassesstowhatextentandthroughwhichmechanisms theystimulateendogenousGABArelease. Methodology/Findings: All agonists elicited GABA overflow. Choline (Ch)-evoked GABA overflow was dependent to 2+ 2+ externalCa ,butunalteredinthepresenceofCd ,tetrodotoxin(TTX),dihydro-b-erythroidine(DHbE)and1-(4,4-Diphenyl- 3-butenyl)-3-piperidinecarboxylic acid hydrochloride SKF 89976A. The effect of Ch was blocked by methyllycaconitine (MLA), a-bungarotoxin (a-BTX), dantrolene, thapsigargin and xestospongin C, suggesting that GABA release might be 2+ triggered by Ca entry into synaptosomes through the a7 nAChR channel with the involvement of calcium from intracellular stores. Additionally, 5-Iodo-A-85380 dihydrochloride (5IA85380) elicited GABA overflow, which was Ca dependent,blockedbyCd ,andsignificantlyinhibitedbyTTXandDHbE,butunaffectedbyMLA,SKF89976A,thapsigargin andxestosponginCanddantrolene.Thesefindingsconfirmtheinvolvementofa4b2nAChRin5IA85380-inducedGABA releasethatseemstooccurfollowingmembranedepolarizationandopeningcalciumchannels. 2+ 2+ Conclusions/Significance: Rat hippocampal synaptosomes possess both a7 and a4b2 nAChR subtyp