Evidence map›Paper›PMID 24762058›Full record

ArticleBritish journal of pharmacology2014

Activation of GPR18 by cannabinoid compounds: a tale of biased agonism.

Linda Console-Bram, Eugen Brailoiu, Gabriela Cristina Brailoiu, Haleli Sharir, Mary E Abood

Open access · bronzeAbstract read
In one paragraph

Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
10.4field-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

83 citing papers in PubMed, 155 citations in OpenAlex.

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  10. Resolvin D2 limits atherosclerosis progression via myeloid cell-GPR18.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  11. Review
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  19. Pharmacognosy and Effects of Cannabinoids in the Vascular System.ACS pharmacology & translational science · 2022
    Review
  20. Article

23 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

5 authors at 1 institution in 1 country.

Linda Console-BramCenter for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA.
Eugen Brailoiu
Gabriela Cristina Brailoiu
Haleli Sharir
Mary E Abood
Temple University · US

Funding

Pilot Projects Core (PPC)P30DA013429 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI Anjali M Rajadhyaksha · 2000 to 2026
$34.6M
TRAINING PROGRAM: DRUGS OF ABUSE RELATED NEUROPEPTIDEST32DA007237 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI ELLEN M UNTERWALD · 1988 to 2026
$10.6M
Molecular Characterization of GPR35 and GPR55, Putative Cannabinoid ReceptorsR01DA023204 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI ABOOD, MARY E · 2007 to 2016
$3.2M
NIDA NIH HHS P30 DA013429NIDA NIH HHS P30DA013429NIDA NIH HHS R01 DA023204NIDA NIH HHS R01DA023204NIDA NIH HHS T32 DA007237NIDA NIH HHS T32DA007237
6 · The paper itself

Abstract

background and purposeGPR18 is a candidate cannabinoid receptor, but its classification as such is controversial. The rationale of the study presented herein was to consider the effects of N-arachidonoyl glycine (NAGly) and cannabinoids via differential G-protein coupled pathways, in addition to β-arrestin signalling. Cellular localization of GPR18 receptors was also examined. EXPERIMENTAL APPROACH: Calcium mobilization and ERK1/2 phosphorylation were quantified in a cell line stably expressing GPR18 (HEK293/GPR18 cells). In addition, using the DiscoveRx PathHunter CHO-K1 GPR18 β-arrestin cell line, recruitment of β-arrestin was quantified. KEY

resultsConcentration-dependent increases in intracellular calcium and ERK1/2 phosphorylation were observed in the presence of NAGly, abnormal cannabidiol (AbnCBD), O-1602, O-1918 and Δ(9)-tetrahydrocannabinol (Δ(9)-THC) in HEK293/GPR18 cells. The initial rise in intracellular calcium in the presence of NAGly, O1918 and THC was blocked by either Gα(q) or Gα(i/o) inhibition. The ERK1/2 phosphorylation was inhibited by Pertussis toxin and N-arachidonoyl-L-serine (NARAS). Recruitment of β-arrestin in the PathHunter CHO-K1 GPR18 cell line revealed a differential pattern of GPR18 activation; of all the ligands tested, only Δ(9)-THC produced a concentration-dependent response. The localization of GPR18 receptors within the HEK293/GPR18 cells is both intracellular, and on the plasma membrane. CONCLUSIONS AND IMPLICATIONS: These findings suggest that GPR18 activation involves several signal transduction pathways indicative of biased agonism, thereby providing a plausible explanation for the apparent discrepancies in GPR18 activation found in the literature. Additionally, the results presented herein provide further evidence for GPR18 as a candidate cannabinoid receptor.

Indexed as

AnimalsArachidonic AcidsArrestinsbeta-ArrestinsCalciumCannabidiolCannabinoid Receptor AgonistsCHO CellsCricetulusCyclohexanesDronabinolGlycineHEK293 CellsHumansMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 34-(3-3,4-p-menthadien-(1,8)-yl)olivetolArachidonic AcidsArrestinsbeta-ArrestinsCalciumCannabidiolCannabinoid Receptor AgonistsCyclohexanesDronabinolGlycineGPR18 protein, humanMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3N-arachidonylglycineO-1602 compoundReceptors, G-Protein-CoupledResorcinols

Identifiers

PMID24762058
PMCPMC4128052
OpenAlexW1504900766

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.