Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system.
By D. Schoepp. Journal of Pharmacology and Experimental Therapeutics, 2001
727 citations recorded by the source corpus.
Metabotropic glutamate (mGlu) receptors, which include mGlu1-8 receptors, are a heterogeneous family of G-protein-coupled receptors which function to modulate brain excitability via presynaptic, postsynaptic and glial mechanisms. Certain members of this receptor family have been shown to function as presynaptic regulatory mechanisms to control release of neurotransmitters. In general, Gi-coupled mGlu receptor subtypes appear to negatively modulate excitatory (and possibly also inhibitory) neurotransmitter output when activated. Localization studies have shown that mGlu7 is restricted to the presynaptic grid at the site of vesicle fusion. These studies along with other evidence suggest that mGlu7 is the nerve terminal autoreceptor that regulates physiological release of glutamate. Other mGlu subtypes, in particular mGlu2, mGlu8, and possibly mGlu4, are also localized presynaptically, but at perisynaptic sites outside the active zone of neurotransmitter release. Gi-coupled mGlu receptors also may exist on presynaptic elements of neighboring gamma-aminobutyric acid (GABA) neurons where they play a role in heterosynaptic suppressions of GABA release. This suggests that these receptors may have evolved to monitor glutamate that has "spilled" out of the synapse. Thus, they may serve as the brain's evolutionary mechanism to prevent pathological changes in neuronal excitability and thus maintain homeostasis. Recent progress on the molecular and pharmacological aspects of these presynaptic mGlu receptors is unveiling their functions and the therapeutic directions of agents designed for these novel glutamate receptor targets.
Subfields: Cellular and Molecular Neuroscience, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/008db3d8c2e437bf7fee6f04a6bb6d36557a850e
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cellular and Molecular Neuroscience
In Molecular Biology
Citations in the corpus
- Metabotropic glutamate receptors as novel targets for anxiety and stress disorders (2005, background): “A growing body of evidence indicates that these receptors might serve as potential therapeutic targets for a variety of pathological state”
- Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial (2007, background): “This agent is thought to work in part by reducing the presynaptic release of glutamate at limbic synapses where these receptors are expresse”
- Neuropeptide transmission in brain circuits (2012, background): “…and interestingly, are expressed in different regions of different neurons. mGluR7, for instance, is often found at the presynaptic active zone (Schoepp,2001) and mGluR4,-7α, and -8α are found on the presynaptic active zone of inhibitory axons, and only those innervating other GABA…”