ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2007
MrgD activation inhibits KCNQ/M-currents and contributes to enhanced neuronal excitability.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Pooled it
- Suppression of neuropathic pain hypersensitivity by TRPM8 is mediated by mGluR group II and III receptors acting differentially on distinct nociceptor inputs to spinal cord.Frontiers in pharmacology · 2026Article
- A perspective on small molecules targeting the renin-angiotensin-aldosterone system and their utility in cardiovascular diseases: exploring the structural insights for rational drug discovery and development.RSC medicinal chemistry · 2025Review
- TET1 Participates in Complete Freund's Adjuvant-induced Trigeminal Inflammatory Pain by Regulating Kv7.2 in a Mouse Model.Neuroscience bulletin · 2024Article
- Review
- KAmerican journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Antihypertensive drugs and brain function: mechanisms underlying therapeutically beneficial and harmful neuropsychiatric effects.Cardiovascular research · 2023Review
- Effect of a sustained-release formulation of β-alanine on laboratory parameters and paresthesia in recreational trained men: a randomized double-blind placebo-controlled study.Frontiers in nutrition · 2023Article
- Structural insight into the activation mechanism of MrgD with heterotrimeric Gi-protein revealed by cryo-EM.Communications biology · 2022Article
- Constitutive, Basal, and β-Alanine-Mediated Activation of the Human Mas-Related G Protein-Coupled Receptor D Induces Release of the Inflammatory Cytokine IL-6 and Is Dependent on NF-κB Signaling.International journal of molecular sciences · 2021Article
- The angiotensin converting enzyme 2 (ACE2) system in the brain: possible involvement in Neuro-Covid.Histology and histopathology · 2021Review
- Increased Bioavailability of β-Alanine by a Novel Controlled-Release Powder Blend Compared to a Slow-Release Tablet.Pharmaceutics · 2021Article
- The signaling pathway and polymorphisms of Mrgprs.Neuroscience letters · 2021Review
- Kv7 Channels and Excitability Disorders.Handbook of experimental pharmacology · 2021Article
- Peripheral Somatosensory Neuron Dysfunction: Emerging Roles in Autism Spectrum Disorders.Neuroscience · 2020Review
- The Role of Amino Acids in Neurotransmission and Fluorescent Tools for Their Detection.International journal of molecular sciences · 2020Review
- 24-Week β-alanine ingestion does not affect muscle taurine or clinical blood parameters in healthy males.European journal of nutrition · 2020Article
- Inhibition of M/KFrontiers in molecular neuroscience · 2020Article
- Expression and localization of MrgprD in mouse intestinal tract.Cell and tissue research · 2019Article
- Nociceptor Signalling through ion Channel Regulation via GPCRs.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The recently identified Mas-related gene (Mrg) family of G-protein-coupled receptors is expressed almost exclusively in dorsal root ganglion (DRG) neurons. The expression of one family member, MrgD, is even further confined to IB4+, nonpeptidergic, small-diameter nociceptors. Although the functional consequences of MrgD activation are not known, this expression profile provides intriguing potential for a role in pain sensation or modulation. In a recombinant cell line, we first assessed the functional significance of MrgD activation by coexpressing MrgD with the KCNQ2/3 potassium channel, a channel implicated in pain. Whole-cell voltage-clamp recordings revealed that bath application of the ligand for MrgD, beta-alanine, resulted in robust inhibition of KCNQ2/3 activity. Pharmacological blockade of G(i/o) and phospholipase C signaling revealed a partial and complete block of the response, respectively. We extended these observations to dissociated DRG neuron cultures by examining MrgD modulation of M-currents (carried primarily by KCNQ2/3). Here too, beta-alanine-induced activation of endogenous MrgD inhibited M-currents, but primarily via a pertussis toxin-sensitive pathway. Finally, we assessed the consequence of beta-alanine-induced activation of MrgD in phasic neurons. Phasic neurons that fired a single action potential (AP) before beta-alanine application fired multiple APs during beta-alanine exposure. In sum, we provide evidence for a novel interaction between MrgD and KCNQ/M-type potassium channels that contributes to an increase in excitability of DRG neurons and thus may enhance the signaling of primary afferent nociceptive neurons.
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