Linked Life Data

21368036

Source:http://linkedlifedata.com/resource/pubmed/id/21368036

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pubmed-article:21368036pubmed:dateCreated2011-3-3lld:pubmed
pubmed-article:21368036pubmed:abstractTextActivation of both presynaptic metabotropic cannabinoid type 1 receptors (CB(1)s) and ionotropic kainate receptors (KARs) can efficiently modulate GABA release at many synapses of the CNS. The inhibitory effect of kainic acid (KA) has been ascribed to metabotropic actions, and KAR-induced release of secondary neuromodulatory agents may partly mediate these actions. Here, we investigated the involvement of the endocannabinoid system in the modulation of GABAergic synaptic transmission by pharmacological activation of KARs with KA in CA1 pyramidal neurons of the mouse hippocampus. We show that the depression of GABAergic synaptic transmission induced by KA (3 ?m) is strongly inhibited by the simultaneous blockade of CB(1) and GABA(B) receptors with SR141716A (5 ?m) and CGP55845 (5 ?m), respectively. KA induces a calcium-dependent mobilization of the endocannabinoid anandamide (AEA) by activation of GluK2-containing KARs in postsynaptic pyramidal neurons. Consistently, the effect of KA is prolonged by the inhibitor of AEA degradation URB597 (1 ?m) in a CB(1)-dependent manner, but it is not altered by blockade of degradation or synthesis of the other main endocannabinoid 2-arachidonoylglycerol (2AG). Hence, our work reveals that the pharmacological activation of KARs leads to the stimulation of secondary metabotropic signaling systems. In addition, these data further underline the profound mechanistic differences between exogenous and endogenous activation of KARs in the hippocampus.lld:pubmed
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pubmed-article:21368036pubmed:authorpubmed-author:MarsicanoGiov...lld:pubmed
pubmed-article:21368036pubmed:authorpubmed-author:MulleChristop...lld:pubmed
pubmed-article:21368036pubmed:authorpubmed-author:MatiasIsabelIlld:pubmed
pubmed-article:21368036pubmed:authorpubmed-author:LourençoJoana...lld:pubmed
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pubmed-article:21368036pubmed:volume31lld:pubmed
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pubmed-article:21368036pubmed:year2011lld:pubmed
pubmed-article:21368036pubmed:articleTitlePharmacological activation of kainate receptors drives endocannabinoid mobilization.lld:pubmed
pubmed-article:21368036pubmed:affiliationINSERM U862 NeuroCentre Magendie, "Endocannabinoids and Neuroadaptation," 33077 Bordeaux, France.lld:pubmed
pubmed-article:21368036pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:21368036pubmed:publicationTypeComparative Studylld:pubmed
pubmed-article:21368036pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed