ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Synaptic Zn2+ inhibits neurotransmitter release by promoting endocannabinoid synthesis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed.
- Metal Ions Within the Neuro-Immune-Tumor Axis.Journal of immunology research · 2026Review
- Exogenous nanomolar zinc ion (ZnBiometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Article
- Cholesterol-Lowering Treatment Suppresses Neuromuscular Transmission Via Presynaptic Mechanism at the Mouse Diaphragm Muscle.Neurochemical research · 2025Article
- Article
- Investigating the role of GPR39 in treatment of stress-induced depression and anxiety.Psychopharmacology · 2025Article
- The Astrocytic Zinc Transporter ZIP12 Is a Synaptic Protein That Contributes to Synaptic Zinc Levels in the Mouse Auditory Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- The zinc receptor, ZnR/GPR39, modulates taste sensitivity by regulating ion secretion in mouse salivary gland.iScience · 2025Article
- Loss of the zinc receptor ZnR/GPR39 in mice enhances anxiety-related behavior and motor deficits, and modulates KCC2 expression in the amygdala.Behavioral and brain functions : BBF · 2024Article
- On the genesis and unique functions of zinc neuromodulation.Journal of neurophysiology · 2024Review
- GPR39 Knockout Worsens Microcirculatory Response to Experimental Stroke in a Sex-Dependent Manner.Translational stroke research · 2023Article
- Synaptic zinc potentiates AMPA receptor function in mouse auditory cortex.Cell reports · 2023Article
- A CRE/DRE dual recombinase transgenic mouse reveals synaptic zinc-mediated thalamocortical neuromodulation.Science advances · 2023Article
- The role of GPR39 zinc receptor in the modulation of glutamatergic and GABAergic transmission.Pharmacological reports : PR · 2023Article
- Zinc and Central Nervous System Disorders.Nutrients · 2023Review
- TC-G 1008 facilitates epileptogenesis by acting selectively at the GPR39 receptor but non-selectively activates CREB in the hippocampus of pentylenetetrazole-kindled mice.Cellular and molecular life sciences : CMLS · 2023Article
- A genetically encoded far-red fluorescent indicator for imaging synaptically released ZnScience advances · 2023Article
- Neuronal signalling of zinc: from detection and modulation to function.Open biology · 2022Review
- The ZIP3 Zinc Transporter Is Localized to Mossy Fiber Terminals and Is Required for Kainate-Induced Degeneration of CA3 Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Role of GPR39 in Neurovascular Homeostasis and Disease.International journal of molecular sciences · 2021Review
- The Zinc-Sensing Receptor GPR39 in Physiology and as a Pharmacological Target.International journal of molecular sciences · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors.
Funding
Abstract
Although it is well established that many glutamatergic neurons sequester Zn(2+) within their synaptic vesicles, the physiological significance of synaptic Zn(2+) remains poorly understood. In experiments performed in a Zn(2+)-enriched auditory brainstem nucleus--the dorsal cochlear nucleus--we discovered that synaptic Zn(2+) and GPR39, a putative metabotropic Zn(2+)-sensing receptor (mZnR), are necessary for triggering the synthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). The postsynaptic production of 2-AG, in turn, inhibits presynaptic probability of neurotransmitter release, thus shaping synaptic strength and short-term synaptic plasticity. Zn(2+)-induced inhibition of transmitter release is absent in mutant mice that lack either vesicular Zn(2+) or the mZnR. Moreover, mass spectrometry measurements of 2-AG levels reveal that Zn(2+)-mediated initiation of 2-AG synthesis is absent in mice lacking the mZnR. We reveal a previously unknown action of synaptic Zn(2+): synaptic Zn(2+) inhibits glutamate release by promoting 2-AG synthesis.
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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.