ArticleNeuropharmacology2010
The PLC/IP 3 R/PKC pathway is required for ethanol-enhanced GABA release.
Article in Neuropharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Synaptic Effects Induced by Alcohol.Current topics in behavioral neurosciences · 2025Review
- Identification of novel genetic loci and candidate genes for progressive ethanol consumption in diversity outbred mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- PLCγ1 in dopamine neurons critically regulates striatal dopamine release via VMAT2 and synapsin III.Experimental & molecular medicine · 2023Article
- The Role of Phospholipase C in GABAergic Inhibition and Its Relevance to Epilepsy.International journal of molecular sciences · 2021Review
- Article
- Mini-Review: Effects of Ethanol on GABAA Receptor-Mediated Neurotransmission in the Cerebellar Cortex--Recent Advances.Cerebellum (London, England) · 2015Review
- Increased voluntary ethanol consumption and changes in hippocampal synaptic plasticity in isolated C57BL/6J mice.Neurochemical research · 2014Review
- Effects of ethanol on glycinergic synaptic currents in mouse spinal cord neurons.Journal of neurophysiology · 2014Article
- Ethanol, not detectably metabolized in brain, significantly reduces brain metabolism, probably via action at specific GABA(A) receptors and has measureable metabolic effects at very low concentrations.Journal of neurochemistry · 2014Article
- Salicylic acid modulates levels of phosphoinositide dependent-phospholipase C substrates and products to remodel the Arabidopsis suspension cell transcriptome.Frontiers in plant science · 2014Article
- Elevated expression patterns and tight correlation of the PLCE1 and NF-κB signaling in Kazakh patients with esophageal carcinoma.Medical oncology (Northwood, London, England) · 2014Article
- Brief alcohol exposure alters transcription in astrocytes via the heat shock pathway.Brain and behavior · 2013Article
- The Arabidopsis DREB2 genetic pathway is constitutively repressed by basal phosphoinositide-dependent phospholipase C coupled to diacylglycerol kinase.Frontiers in plant science · 2013Article
- HSF1 transcriptional activity mediates alcohol induction of Vamp2 expression and GABA release.Frontiers in integrative neuroscience · 2013Article
- Synaptic effects induced by alcohol.Current topics in behavioral neurosciences · 2013Review
- Ultrastructure of synapses in the mammalian brain.Cold Spring Harbor perspectives in biology · 2012Review
- Neuropeptide modulation of central amygdala neuroplasticity is a key mediator of alcohol dependence.Neuroscience and biobehavioral reviews · 2012Review
- Ethanol modulation of synaptic plasticity.Neuropharmacology · 2011Review
- Voluntary Ethanol Consumption Induced by Social Isolation Reverses the Increase of α(4)/δ GABA(A) Receptor Gene Expression and Function in the Hippocampus of C57BL/6J Mice.Frontiers in neuroscience · 2011Article
- Ethanol-enhanced GABA release: a focus on G protein-coupled receptors.Brain research reviews · 2011Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Research on the actions of ethanol at the GABAergic synapse has traditionally focused on postsynaptic mechanisms, but recent data demonstrate that ethanol also increases both evoked and spontaneous GABA release in many brain regions. Using whole-cell voltage-clamp recordings, we previously showed that ethanol increases spontaneous GABA release at the rat interneuron-Purkinje cell synapse. This presynaptic ethanol effect is dependent on calcium release from internal stores, possibly through activation of inositol 1,4,5-trisphosphate receptors (IP(3)Rs). After confirming that ethanol targets vesicular GABA release, in the present study we used electron microscopic immunohistochemistry to demonstrate that IP(3)Rs are located in presynaptic terminals of cerebellar interneurons. Activation of IP(3)Rs requires binding of IP(3), generated through activation of phospholipase C (PLC). We find that the PLC antagonist edelfosine prevents ethanol from increasing spontaneous GABA release. Diacylglycerol generated by PLC and calcium released by activation of the IP(3)R activate protein kinase C (PKC). Ethanol-enhanced GABA release was blocked by two PKC antagonists, chelerythrine and calphostin C. When a membrane impermeable PKC antagonist, PKC (19-36), was delivered intracellularly to the postsynaptic neuron, ethanol continued to increase spontaneous GABA release. Overall, these results suggest that activation of the PLC/IP(3)R/PKC pathway is necessary for ethanol to increase spontaneous GABA release from presynaptic terminals onto Purkinje cells.
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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.