Evidence map›Paper›PMID 30202012›Full record

ArticleActa pharmacologica Sinica2019

Identification of novel mouse and rat CB1R isoforms and in silico modeling of human CB1R for peripheral cannabinoid therapeutics.

Qing-Rong Liu, Nicholas S Huang, Hong Qu, Jennifer F O'Connell, Isabel Gonzalez-Mariscal, Sara Santa-Cruz-Calvo, Maire E Doyle, Zheng-Xiong Xi, Yun Wang, Emmanuel S Onaivi and 1 more

Open access · hybridAbstract read
In one paragraph

Article 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 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 15% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. Dissecting the role of CBEuropean neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2021
    Article
  7. Review
  8. Article
  9. Neurobiology of cannabinoid receptor signaling
.Dialogues in clinical neuroscience · 2020
    Review
  10. Article
  11. Article
  12. Article
  13. Article
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

11 authors at 5 institutions in 3 countries.

Qing-Rong LiuLaboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, MD, USA. qliu@mail.nih.gov.
Nicholas S HuangLaboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, MD, USA.
Hong QuCenter for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing, China.
Jennifer F O'ConnellLaboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, MD, USA.
Isabel Gonzalez-MariscalLaboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, MD, USA.
Sara Santa-Cruz-CalvoLaboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, MD, USA.
Maire E DoyleLaboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, MD, USA.
Zheng-Xiong XiAddiction Biology Unit, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, NIH, Baltimore, MD, USA.
Yun WangCenter for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.
Emmanuel S OnaiviDepartment of Biology, William Paterson University, Wayne, NJ, USA.
Josephine M EganLaboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, MD, USA.
National Institute on Aging · USNational Health Research Institutes · TWNational Institute on Drug Abuse · USPeking University · CNWilliam Paterson University · US

Funding

Central CB2 Cannabinoid ReceptorsZIADA000620 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI NEWMAN, AMY HAUCK · 2017 to 2019
$860k
BEHAVIORAL EFFECTS OF CB2 CANNABINOID RECEPTORS (CB2RS)R15DA032890 · NIDA · WILLIAM PATERSON UNIVERSITY · PI ONAIVI, EMMANUEL S · 2012 to 2012
$352k
NIDA NIH HHS R15 DA032890
6 · The paper itself

Abstract

Targeting peripheral CB1R is desirable for the treatment of metabolic syndromes without adverse neuropsychiatric effects. We previously reported a human hCB1b isoform that is selectively enriched in pancreatic beta-cells and hepatocytes, providing a potential peripheral therapeutic hCB1R target. It is unknown whether there are peripherally enriched mouse and rat CB1R (mCB1 and rCB1, respectively) isoforms. In this study, we found no evidence of peripherally enriched rodent CB1 isoforms; however, some mCB1R isoforms are absent in peripheral tissues. We show that the mouse Cnr1 gene contains six exons that are transcribed from a single promoter. We found that mCB1A is a spliced variant of extended exon 1 and protein-coding exon 6; mCB1B is a novel spliced variant containing unspliced exon 1, intron 1, and exon 2, which is then spliced to exon 6; and mCB1C is a spliced variant including all 6 exons. Using RNAscope in situ hybridization, we show that the isoforms mCB1A and mCB1B are expressed at a cellular level and colocalized in GABAergic neurons in the hippocampus and cortex. RT-qPCR reveals that mCB1A and mCB1B are enriched in the brain, while mCB1B is not expressed in the pancreas or the liver. Rat rCB1R isoforms are differentially expressed in primary cultured neurons, astrocytes, and microglia. We also investigated modulation of Cnr1 expression by insulin in vivo and carried out in silico modeling of CB1R with JD5037, a peripherally restricted CB1R inverse agonist, using the published crystal structure of hCB1R. The results provide models for future CB1R peripheral targeting.

Indexed as

Amino Acid SequenceAnimalsArachidonic AcidsCannabinoid Receptor AgonistsCerebral CortexEndocannabinoidsExonsGlyceridesHumansMaleMice, Inbred C57BLMolecular Docking SimulationPromoter Regions, GeneticProtein IsoformsPyrazolesRats, Long-EvansArachidonic AcidsCannabinoid Receptor AgonistsEndocannabinoidsGlyceridesglyceryl 2-arachidonateJD5037Protein IsoformsPyrazolesReceptor, Cannabinoid, CB1Sulfonamidesalternative splicingcannabinoidscell- and tissue-based therapygene expression

Identifiers

PMID30202012
PMCPMC6460360
OpenAlexW2891148362

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.