ArticleThe Journal of biological chemistry2010
Sustained glutamate receptor activation down-regulates GABAB receptors by shifting the balance from recycling to lysosomal degradation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 57 citations in OpenAlex.
- The E3 ubiquitin ligase MARCH1 mediates downregulation of plasma membrane GABAScientific reports · 2025Article
- Pharmacological mechanism and clinical application of ciprofol.Frontiers in pharmacology · 2025Review
- Optimization of neuron-specific interfering peptides targeting GABAFrontiers in pharmacology · 2025Article
- Restoring GABAFrontiers in molecular neuroscience · 2024Article
- ERK1/2-Dependent Phosphorylation of GABAInternational journal of molecular sciences · 2023Article
- Ethanol blocks a novel form of iLTD, but not iLTP of inhibitory inputs to VTA GABA neurons.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Targeting the interaction of GABABrain pathology (Zurich, Switzerland) · 2023Article
- Medial prefrontal cortex Notch1 signalling mediates methamphetamine-induced psychosis via Hes1-dependent suppression of GABAMolecular psychiatry · 2022Article
- Article
- Mechanisms and Regulation of Neuronal GABACurrent topics in behavioral neurosciences · 2022Review
- Protein phosphatase 2A regulation of GABAFrontiers in molecular neuroscience · 2022Article
- Targeting the Interaction of GABAFrontiers in pharmacology · 2022Article
- GABACurrent topics in behavioral neurosciences · 2022Review
- Reelin signaling modulates GABAJournal of neurochemistry · 2021Article
- Sustained Baclofen-Induced Activation of GABAFrontiers in molecular neuroscience · 2021Article
- Cross-modal reaction of auditory and visual cortices after long-term bilateral hearing deprivation in the rat.Brain structure & function · 2020Article
- CaMolecular neurobiology · 2019Article
- Long-Term Stress Disrupts the Structural and Functional Integrity of GABAergic Neuronal Networks in the Medial Prefrontal Cortex of Rats.Frontiers in cellular neuroscience · 2018Article
- Neuroadaptations of presynaptic and postsynaptic GABABritish journal of pharmacology · 2017Article
- GABAb Receptor Mediates Opposing Adaptations of GABA Release From Two Types of Prefrontal Interneurons After Observational Fear.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabotropic GABA(B) receptors are abundantly expressed at glutamatergic synapses where they control excitability of the synapse. Here, we tested the hypothesis that glutamatergic neurotransmission may regulate GABA(B) receptors. We found that application of glutamate to cultured cortical neurons led to rapid down-regulation of GABA(B) receptors via lysosomal degradation. This effect was mimicked by selective activation of AMPA receptors and further accelerated by coactivation of group I metabotropic glutamate receptors. Inhibition of NMDA receptors, blockade of L-type Ca(2+) channels, and removal of extracellular Ca(2+) prevented glutamate-induced down-regulation of GABA(B) receptors, indicating that Ca(2+) influx plays a critical role. We further established that glutamate-induced down-regulation depends on the internalization of GABA(B) receptors. Glutamate did not affect the rate of GABA(B) receptor endocytosis but led to reduced recycling of the receptors back to the plasma membrane. Blockade of lysosomal activity rescued receptor recycling, indicating that glutamate redirects GABA(B) receptors from the recycling to the degradation pathway. In conclusion, the data indicate that sustained activation of AMPA receptors down-regulates GABA(B) receptors by sorting endocytosed GABA(B) receptors preferentially to lysosomes for degradation on the expense of recycling. This mechanism may relieve glutamatergic synapses from GABA(B) receptor-mediated inhibition resulting in increased synaptic excitability.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.