Pharmacological activation of kainate receptors drives endocannabinoid mobilization
Journal of Neuroscience. 2011-03-02; 31(9): 3243-3248
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1. J Neurosci. 2011 Mar 2;31(9):3243-8. doi: 10.1523/JNEUROSCI.3512-10.2011.
Pharmacological activation of kainate receptors drives endocannabinoid
Lourenço J(1), Matias I, Marsicano G, Mulle C.
(1)INSERM U862 NeuroCentre Magendie, « Endocannabinoids and Neuroadaptation, »
33077 Bordeaux, France.
Activation 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 μm) is strongly inhibited by the
simultaneous blockade of CB(1) and GABA(B) receptors with SR141716A (5 μm) and
CGP55845 (5 μm), 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 μm) 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.
PMID: 21368036 [Indexed for MEDLINE]