Evidence map›Paper›PMID 16954222›Full record

ArticleThe Journal of biological chemistry2006

Cannabinoid WIN 55,212-2 regulates TRPV1 phosphorylation in sensory neurons.

Nathaniel A Jeske, Amol M Patwardhan, Nikita Gamper, Theodore J Price, Armen N Akopian, Kenneth M Hargreaves

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
5.7field-weighted citation impact, top 3% 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, 142 citations in OpenAlex.

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  12. Roles of TRP Channels in Neurological Diseases.Oxidative medicine and cellular longevity · 2020
    Review
  13. Sensitization of small-diameter sensory neurons is controlled by TRPV1 and TRPA1 association.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  14. Article
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  16. Review
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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

6 authors at 3 institutions in 2 countries.

Nathaniel A JeskeDepartments of Endodontics, Pharmacology, and Physiology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Amol M Patwardhan
Nikita Gamper
Theodore J Price
Armen N Akopian
Kenneth M Hargreaves
The University of Texas Health Science Center at San Antonio · USAmerican Association of Endodontists · USNational Medical Research Center of Dentistry and Maxillofacial Surgery · RU

Funding

Cannabinoid Modulation of Capsaicin-Sensitive NociceptorsR01DA019585 · NIDA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI HARGREAVES, KENNETH M · 2006 to 2010
$1.4M
Mechanisms of Nociceptive Neuronal PlasticityR21DE014928 · NIDCR · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · PI AKOPIAN, ARMEN N · 2003 to 2004
$292k
Cannabinoid-Induced Desensitization of TRPV1 ReceptorsF32DE016500 · NIDCR · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI JESKE, NATHANIEL AARON · 2005 to 2006
$80k
PERIPHERAL MECHANISMS OF CANNABINOID ANTINOCICEPTIONF31DA006085 · NIDA · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · PI PRICE, THEODORE J · 2000 to 2002
$64k
NIDA NIH HHS F31 DA006085NIDA NIH HHS R01 DA019585NIDA NIH HHS R01 DA 19585NIDCR NIH HHS F32 DE 016500NIDCR NIH HHS F32 DE016500NIDCR NIH HHS R21 DE 014928NIDCR NIH HHS R21 DE014928
6 · The paper itself

Abstract

Cannabinoids are known to have multiple sites of action in the nociceptive system, leading to reduced pain sensation. However, the peripheral mechanism(s) by which this phenomenon occurs remains an issue that has yet to be resolved. Because phosphorylation of TRPV1 (transient receptor potential subtype V1) plays a key role in the induction of thermal hyperalgesia in inflammatory pain models, we evaluated whether the cannabinoid agonist WIN 55,212-2 (WIN) regulates the phosphorylation state of TRPV1. Here, we show that treatment of primary rat trigeminal ganglion cultures with WIN led to dephosphorylation of TRPV1, specifically at threonine residues. Utilizing Chinese hamster ovary cell lines, we demonstrate that Thr(144) and Thr(370) were dephosphorylated, leading to desensitization of the TRPV1 receptor. This post-translational modification occurred through activation of the phosphatase calcineurin (protein phosphatase 2B) following WIN treatment. Furthermore, knockdown of TRPA1 (transient receptor potential subtype A1) expression in sensory neurons by specific small interfering RNA abolished the WIN effect on TRPV1 dephosphorylation, suggesting that WIN acts through TRPA1. We also confirm the importance of TRPA1 in WIN-induced dephosphorylation of TRPV1 in Chinese hamster ovary cells through targeted expression of one or both receptor channels. These results imply that the cannabinoid WIN modulates the sensitivity of sensory neurons to TRPV1 activation by altering receptor phosphorylation. In addition, our data could serve as a useful strategy in determining the potential use of certain cannabinoids as peripheral analgesics.

Indexed as

AnimalsAnkyrinsBenzoxazinesCalcineurinCalcium ChannelsCannabinoidsCells, CulturedCHO CellsCollagenasesCricetinaeElectroporationEnzyme ActivationMaleMorpholinesNaphthalenesNeurons, Afferent(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanoneAnkyrinsBenzoxazinesCalcineurinCalcium ChannelsCannabinoidsCollagenasesMorpholinesNaphthalenesRNA, Small InterferingThreonineTRPA1 Cation ChannelTrpa1 protein, ratTRPC Cation ChannelsTRPV1 receptorTRPV Cation ChannelsTrypsin

Identifiers

PMID16954222
PMCPMC2910918
OpenAlexW1991417446

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.