Cited by 775Ion Channels and ReceptorsCannabis and Cannabinoid ResearchPain Mechanisms and Treatments

The endogenous lipid anandamide is a full agonist at the human vanilloid receptor (hVR1)

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Smart, D, Gunthorpe, M J, Jerman, J C, Nasir, S, Gray, J, Muir, A I, Chambers, J K, Randall, A D +1 more·2000·British Journal of Pharmacology

Abstract

The endogenous cannabinoid anandamide was identified as an agonist for the recombinant human VR1 (hVR1) by screening a large array of bioactive substances using a FLIPR-based calcium assay. Further electrophysiological studies showed that anandamide (10 or 100 microM) and capsaicin (1 microM) produced similar inward currents in hVR1 transfected, but not in parental, HEK293 cells. These currents were abolished by capsazepine (1 microM). In the FLIPR anandamide and capsaicin were full agonists at hVR1, with pEC(50) values of 5. 94+/-0.06 (n=5) and 7.13+/-0.11 (n=8) respectively. The response to anandamide was inhibited by capsazepine (pK(B) of 7.40+/-0.02, n=6), but not by the cannabinoid receptor antagonists AM630 or AM281. Furthermore, pretreatment with capsaicin desensitized the anandamide-induced calcium response and vice versa. In conclusion, this study has demonstrated for the first time that anandamide acts as a full agonist at the human VR1.

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Crossref · 10.1038/sj.bjp.0703050

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  • AEA actions are not restricted to CB1R; ECBs also act at CB2R, GPR55, TRPV1, and other G protein subtypes such as Gs and/or Gq11.

    “Enriching the picture further, the actions of AEA are not restricted to CB1R, given that ECBs also act, sometimes in a non-retrograde manner, at CB2R [30], GPR55 [31], and TRPV1 (transient receptor potential vanilloid type 1) channels [32–34], as well as other G protein subtypes such as Gs and/or Gq11 [35,36].”

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Research works printed but not linked: 1

  1. Lambert, D.G. (ed.). Calcium Signaling Protocols. Humana Press: New Jersey, pp. 125 ± 136.

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Authors
Smart, D., Gunthorpe, M. J., Jerman, J. C., Nasir, S., Gray, J., Muir, A. I., Chambers, J. K., Randall, A. D., & Davis, J. B.
Affiliations
GlaxoSmithKline (United Kingdom) (GB)
Corresponding author
Smart, D
Venue
British Journal of Pharmacology
Publisher
Wiley
Published
2000-01
Volume
129
Issue
2
Pages
227-230
ISSN
  • 0007-1188 (ISSN-L)
  • 1476-5381
OpenAlex
W2022819833
Cited by
775
References
12
Citations by year
2026: 5 · 2025: 11 · 2024: 12 · 2023: 15 · 2022: 19 · 2021: 22 · 2020: 26 · 2019: 18 · 2018: 16 · 2017: 18 · 2016: 15 · 2015: 22 · 2014: 19 · 2013: 20 · 2012: 34
FWCI
27.82
Type
journal article
Language
en
Open access
Locations
  • British Journal of Pharmacology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Keywords
anandamide, vanilloid receptor 1, TRPV1, capsaicin, capsazepine, calcium current, receptor desensitization, endocannabinoids, AM630, AM281
MeSH terms
Amides, Arachidonic Acids, Binding, Competitive, Calcium, Cannabinoids, Capsaicin, Cell Line, Cloning, Molecular, Electrophysiology, Ethanolamines, Humans, Hydrogen-Ion Concentration, Palmitic Acids, Receptors, Drug, Recombinant Proteins, Calcium Channels, Patch-Clamp Techniques, TRPV Cation Channels, Polyunsaturated Alkamides, Endocannabinoids

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