Pharmacological activation of kainate receptors drives endocannabinoid mobilization
Open accessAbstract
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.
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Kainate receptors have been implicated in the mobilization of endocannabinoid signaling in distinct brain regions, as well as in the promotion of GABAergic signaling in the PVN.
“Kainate receptors have been implicated in the mobilization of endocannabinoid signaling in distinct brain regions, as well as in the promotion of GABAergic signaling in the PVN (Evanson and Herman, 2015;Lourenço et al., 2011;Marshall et al., 2018).”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Lourenço et al., 2011
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- Authors
- Lourenço, J., Matias, I., Marsicano, G., & Mulle, C.
- Affiliations
- Inserm (FR)
- Université de Bordeaux (FR)
- Centre National de la Recherche Scientifique (FR)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-03-02
- Volume
- 31
- Issue
- 9
- Pages
- 3243-3248
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6623943
- OpenAlex
- W2083736953
- Cited by
- 46
- References
- 38
- Citations by year
- 2025: 1 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 6 · 2013: 3 · 2012: 6
- FWCI
- 4.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission (223713)
- Agence Nationale de la Recherche (ANR-06-NEUR-0043, ANR-05, ANR-05-NEUR-0033)
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique
- FP7 Ideas: European Research Council (260515)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- kainate receptors, endocannabinoid system, anandamide, CB1 receptor, GABAergic neurotransmission, kainic acid, GluK2, CA1 pyramidal neurons, GABAB receptors, 2-arachidonoylglycerol, URB597, SR141716A, CGP55845, presynaptic inhibition
- MeSH terms
- Rimonabant, GluK2 Kainate Receptor, Animals, Hippocampus, Kainic Acid, Mice, Inbred C57BL, Piperidines, Pyrazoles, Signal Transduction, Receptors, GABA-B, Receptors, Kainic Acid, Kainic Acid Receptors, Mice, Knockout, Receptor Cross-Talk, Receptor, Cannabinoid, CB1, Mice, Cannabinoid Receptor Modulators, Endocannabinoids
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