ArticleMolecular pharmacology2014
Cooperative signaling between homodimers of metabotropic glutamate receptors 1 and 5.
Article in Molecular pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
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- Parvalbumin interneuron mGlubioRxiv : the preprint server for biology · 2024Article
- Targeting metabotropic glutamate receptors for the treatment of depression and other stress-related disorders.Neuropharmacology · 2021Review
- Article
- Mechanisms Underlying Enhancement of Spontaneous Glutamate Release by Group I mGluRs at a Central Auditory Synapse.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Defining the Homo- and Heterodimerization Propensities of Metabotropic Glutamate Receptors.Cell reports · 2020Article
- Transcriptional corepressor SIN3A regulates hippocampal synaptic plasticity via Homer1/mGluR5 signaling.JCI insight · 2020Article
- Inhibitory effects of fucoidan on NMDA receptors and l-type CaPharmaceutical biology · 2019Article
- Target validation: Weak selectivity of LY341495 for mGluR2 over mGluR4 makes glutamate a less selective agonist.Pharmacology research & perspectives · 2019Article
- Kinetic and system bias as drivers of metabotropic glutamate receptor 5 allosteric modulator pharmacology.Neuropharmacology · 2019Article
- Family C G-Protein-Coupled Receptors in Alzheimer's Disease and Therapeutic Implications.Frontiers in pharmacology · 2019Review
- Functional Cross-Talk between Adenosine and Metabotropic Glutamate Receptors.Current neuropharmacology · 2019Review
- Functional partnership between mGlu3 and mGlu5 metabotropic glutamate receptors in the central nervous system.Neuropharmacology · 2018Article
- Biased allosteric agonism and modulation of metabotropic glutamate receptor 5: Implications for optimizing preclinical neuroscience drug discovery.Neuropharmacology · 2017Article
- Metabotropic glutamate receptor subtype 5: molecular pharmacology, allosteric modulation and stimulus bias.British journal of pharmacology · 2016Review
- Group 1 metabotropic glutamate receptors 1 and 5 form a protein complex in mouse hippocampus and cortex.Proteomics · 2016Article
- mGluR1 and mGluR5 Synergistically Control Cholinergic Synaptic Transmission in the Thalamic Reticular Nucleus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Molecular Insights into Metabotropic Glutamate Receptor Allosteric Modulation.Molecular pharmacology · 2015Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Metabotropic glutamate receptors (mGluRs) function as dimers. Recent work suggests that mGluR1 and mGluR5 may physically interact, but the nature and functional consequences of this relationship have not been addressed. In this study, the functional and pharmacological consequences of this interaction were investigated. Using heterologous expression of mGluR cDNA in rat sympathetic neurons from the superior cervical ganglion and inhibition of the native calcium currents as an assay for receptor activation, a functional interdependence between mGluR1 and mGluR5 was demonstrated. In neurons coexpressing these receptors, combining a selective mGluR1 competitive antagonist with either an mGluR1- or mGluR5-selective negative allosteric modulator (NAM) BAY36-7620 [(3aS,6aS)-hexahydro-5-methylene-6a-(2-naphthalenylmethyl)-1H-cyclopenta[c]furan-1-one] or MPEP [2-methyl-6-(phenylethynyl)pyridine hydrochloride], respectively, strongly occluded signaling by both receptors to an approximately equal degree. By contrast, in cells coexpressing mGluR1 and mGluR2, combining the same mGluR1 competitive inhibitor with an mGluR1 or mGluR2 NAM yielded partial and full inhibition of the response, respectively, as expected for independently acting receptors. In neurons expressing mGluR1 and mGluR5, the selective NAMs each strongly inhibited the response to glutamate, suggesting that these receptors do not interact as heterodimers, which would not be inhibited by selective NAMs. Finally, evidence for a similar mGluR1/mGluR5 functional dependence is shown in medium spiny striatal neurons. Together, these data demonstrate cooperative signaling between mGluR1 and mGluR5 in a manner inconsistent with heterodimerization, and thus suggest an interaction between homodimers.
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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.