Evidence map›Paper›PMID 29941868›Full record

ReviewActa pharmacologica Sinica2019

GPR3, GPR6, and GPR12 as novel molecular targets: their biological functions and interaction with cannabidiol.

Alyssa S Laun, Sarah H Shrader, Kevin J Brown, Zhao-Hui Song

Open access · bronzeAbstract readReview
In one paragraph

Review in Acta pharmacologica Sinica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 1 pooled it
9.3field-weighted citation impact, top 1% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 1 synthesis or guideline pooled it, 167 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Cannabidiol-Ion Channel Interactions Represent a Promising Preventive and Therapeutic Strategy in Hepatocellular Carcinoma.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026
    Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. GPCR drug discovery: new agents, targets and indications.Nature reviews. Drug discovery · 2025
    Review
  18. Review
  19. Review
  20. Article

22 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Alyssa S LaunDepartment of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40292, USA.
Sarah H ShraderDepartment of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40292, USA.
Kevin J BrownDepartment of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40292, USA.
Zhao-Hui SongDepartment of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40292, USA. zhsong@louisville.edu.
University of Louisville · US

Funding

UOFL ENVIRONMENTAL HEALTH SCIENCES TRAINING PROGRAMT32ES011564 · NIEHS · UNIVERSITY OF LOUISVILLE · PI David W Hein, John Pierce Wise · 2004 to 2026
$7.1M
University of Louisville Cancer Education ProgramR25CA134283 · NCI · UNIVERSITY OF LOUISVILLE · PI HEIN, DAVID W, KIDD, LA CREIS RENEE · 2011 to 2022
$3.1M
Cannabinoid Receptors and Novel Antiglaucoma DrugsR01EY013632 · NEI · UNIVERSITY OF LOUISVILLE · PI SONG, ZHAO-HUI · 2003 to 2010
$1.9M
Structure and Function of CB2 Cannabinoid ReceptorR01DA011551 · NIDA · UNIVERSITY OF LOUISVILLE · PI SONG, ZHAO-HUI · 2004 to 2008
$1.3M
STRUCTURE/FUNCTION OF CB2 CANNABINOID RECEPTORR29DA011551 · NIDA · UNIVERSITY OF LOUISVILLE · PI SONG, ZHAO-HUI · 1998 to 2002
$307k
NCI NIH HHS R25 CA134283NEI NIH HHS R01 EY013632NIDA NIH HHS R01 DA011551NIDA NIH HHS R29 DA011551NIEHS NIH HHS T32 ES011564
6 · The paper itself

Abstract

The G protein-coupled receptors 3, 6, and 12 (GPR3, GPR6, and GPR12) comprise a family of closely related orphan receptors with no confirmed endogenous ligands. These receptors are constitutively active and capable of signaling through G protein-mediated and non-G protein-mediated mechanisms. These orphan receptors have previously been reported to play important roles in many normal physiological functions and to be involved in a variety of pathological conditions. Although they are orphans, GPR3, GPR6, and GPR12 are phylogenetically most closely related to the cannabinoid receptors. Using β-arrestin2 recruitment and cAMP accumulation assays, we recently found that the nonpsychoactive phytocannabinoid cannabidiol (CBD) is an inverse agonist for GPR3, GPR6, and GPR12. This discovery highlights these orphan receptors as potential new molecular targets for CBD, provides novel mechanisms of action, and suggests new therapeutic uses of CBD for illnesses such as Alzheimer's disease, Parkinson's disease, cancer, and infertility. Furthermore, identification of CBD as a new inverse agonist for GPR3, GPR6, and GPR12 provides the initial chemical scaffolds upon which potent and efficacious agents acting on these receptors can be developed, with the goal of developing chemical tools for studying these orphan receptors and ultimately new therapeutic agents.

Indexed as

AnimalsCannabidiolDrug Inverse AgonismHumansLigandsNeuronsReceptors, G-Protein-CoupledSignal TransductionCannabidiolLigandsReceptors, G-Protein-CoupledAlzheimer’s diseasecannabidioleurite outgrowthGPR12GPR3GPR6infertility.inverse agonistneuropathic painobesityorphan receptors

Identifiers

PMID29941868
PMCPMC6460361
OpenAlexW2810429878

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.