ReviewDrug metabolism reviews2018
Towards a better understanding of the cannabinoid-related orphan receptors GPR3, GPR6, and GPR12.
Review in Drug metabolism reviews, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Endocannabinoid System as a Promising Therapeutic Target in Inflammatory Bowel Disease - A Systematic Review.Frontiers in immunology · 2021Pooled it
- Discovery of Small Molecule Ligands Targeting Orphan G Protein-Coupled Receptors GPR3, GPR6, and GPR12.Journal of medicinal chemistry · 2026Review
- Drug Repurposing: Conversion of the Peripherally Restricted HIV Protease Inhibitor Amprenavir to Potent, Selective, and CNS-Penetrant Agonists for the Cannabinoid Receptor 2.Journal of medicinal chemistry · 2026Article
- Beyond the hype: a comprehensive exploration of CBD's biological impacts and mechanisms of action.Journal of cannabis research · 2025Review
- New MiniPromoter Ple389 (ADORA2A) drives selective expression in medium spiny neurons in mice and non-human primates.Scientific reports · 2024Article
- CVN424, a GPR6 inverse agonist, for Parkinson's disease and motor fluctuations: a double-blind, randomized, phase 2 trial.EClinicalMedicine · 2024Article
- Review
- Structural and functional characterization of the endogenous agonist for orphan receptor GPR3.Cell research · 2024Article
- Exploring orphan GPCRs in neurodegenerative diseases.Frontiers in pharmacology · 2024Review
- Development of Fluorescent AF64394 Analogues Enables Real-Time Binding Studies for the Orphan Class A GPCR GPR3.Journal of medicinal chemistry · 2023Article
- Specific binding of GPR174 by endogenous lysophosphatidylserine leads to high constitutive GNature communications · 2023Article
- Glycine: The Smallest Anti-Inflammatory Micronutrient.International journal of molecular sciences · 2023Review
- The Polypharmacological Effects of Cannabidiol.Molecules (Basel, Switzerland) · 2023Review
- Article
- Glycine Effect on the Expression Profile of Orphan Receptors GPR21, GPR26, GPR39, GPR82 and GPR6 in a Model of Inflammation in 3T3-L1 Cells.Life (Basel, Switzerland) · 2022Article
- The Microbiome and Gut Endocannabinoid System in the Regulation of Stress Responses and Metabolism.Frontiers in cellular neuroscience · 2022Review
- Cellular distribution of cannabinoid-related receptors TRPV1, PPAR-gamma, GPR55 and GPR3 in the equine cervical dorsal root ganglia.Equine veterinary journal · 2021Article
- Article
- Article
- Recent Advances in the Potential of Cannabinoids for Neuroprotection in Alzheimer's, Parkinson's, and Huntington's Diseases.Advances in experimental medicine and biology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
GPR3, GPR6, and GPR12 are three orphan receptors that belong to the Class A family of G-protein-coupled receptors (GPCRs). These GPCRs share over 60% of sequence similarity among them. Because of their close phylogenetic relationship, GPR3, GPR6, and GPR12 share a high percentage of homology with other lipid receptors such as the lysophospholipid and the cannabinoid receptors. On the basis of sequence similarities at key structural motifs, these orphan receptors have been related to the cannabinoid family. However, further experimental data are required to confirm this association. GPR3, GPR6, and GPR12 are predominantly expressed in mammalian brain. Their high constitutive activation of adenylyl cyclase triggers increases in cAMP levels similar in amplitude to fully activated GPCRs. This feature defines their physiological role under certain pathological conditions. In this review, we aim to summarize the knowledge attained so far on the understanding of these receptors. Expression patterns, pharmacology, physiopathological relevance, and molecules targeting GPR3, GPR6, and GPR12 will be analyzed herein. Interestingly, certain cannabinoid ligands have been reported to modulate these orphan receptors. The current debate about sphingolipids as putative endogenous ligands will also be addressed. A special focus will be on their potential role in the brain, particularly under neurological conditions such as Parkinson or Alzheimer's disease. Reported physiological roles outside the central nervous system will also be covered. This critical overview may contribute to a further comprehension of the physiopathological role of these orphan GPCRs, hopefully attracting more research towards a future therapeutic exploitation of these promising targets.
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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.