The endogenous lipid anandamide is a full agonist at the human vanilloid receptor (hVR1)
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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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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].”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [33]
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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
- PMC
- PMC1571834
- 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
- bronze
- doi.org
- 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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