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Cited by 196Cannabis and Cannabinoid ResearchIon Channels and ReceptorsBiochemical and biochemical processes

Unsaturated long-chain N-acyl-vanillyl-amides (N-AVAMs): vanilloid receptor ligands that inhibit anandamide-facilitated transport and bind to CB1 cannabinoid receptors

Melck, Dominique, Bisogno, Tiziana, De Petrocellis, Luciano, Chuang, Huai-hu, Julius, David, Bifulco, Maurizio, Di Marzo, Vincenzo·1999·Biochemical and Biophysical Research Communications
DOI 10.1006/bbrc.1999.1105
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Abstract

We investigated the effect of changing the length and degree of unsaturation of the fatty acyl chain of N-(3-methoxy-4-hydroxy)-benzyl-cis-9-octadecenoamide (olvanil), a ligand of vanilloid receptors, on its capability to: (i) inhibit anandamide-facilitated transport into cells and enzymatic hydrolysis, (ii) bind to CB1 and CB2 cannabinoid receptors, and (iii) activate the VR1 vanilloid receptor. Potent inhibition of [(14)C]anandamide accumulation into cells was achieved with C20:4 n-6, C18:3 n-6 and n-3, and C18:2 n-6 N-acyl-vanillyl-amides (N-AVAMs). The saturated analogues and Delta(9)-trans-olvanil were inactive. Activity in CB1 binding assays increased when increasing the number of cis-double bonds in a n-6 fatty acyl chain and, in saturated N-AVAMs, was not greatly sensitive to decreasing the chain length. The C20:4 n-6 analogue (arvanil) was a potent inhibitor of anandamide accumulation (IC(50) = 3.6 microM) and was 4-fold more potent than anandamide on CB1 receptors (Ki = 0.25-0.52 microM), whereas the C18:3 n-3 N-AVAM was more selective than arvanil for the uptake (IC(50) = 8.0 microM) vs CB1 receptors (Ki = 3.4 microM). None of the compounds efficiently inhibited [(14)C]anandamide hydrolysis or bound to CB2 receptors. All N-AVAMs activated the cation currents coupled to VR1 receptors overexpressed in Xenopus oocytes. In a simple, intact cell model of both vanilloid- and anandamide-like activity, i.e., the inhibition of human breast cancer cell (HBCC) proliferation, arvanil was shown to behave as a "hybrid" activator of cannabinoid and vanilloid receptors.

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Crossref · 10.1006/bbrc.1999.1105

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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 [34]

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Authors
Melck, D., Bisogno, T., De Petrocellis, L., Chuang, H.-H., Julius, D., Bifulco, M., & Di Marzo, V.
Affiliations
  • University of Naples Federico II (IT)
  • National Research Council (IT)
  • University of California, San Francisco (US)
ORCID
Venue
Biochemical and Biophysical Research Communications
Publisher
Elsevier BV
Published
1999-08
Volume
262
Issue
1
Pages
275-284
ISSN
0006-291X (ISSN-L)
DOI
10.1006/bbrc.1999.1105
OpenAlex
W2072730289
Cited by
188
References
37
Citations by year
2026: 2 · 2025: 1 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 3 · 2015: 6 · 2014: 5 · 2013: 5 · 2012: 6
FWCI
11.23
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biochemical and Biophysical Research Communications (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Biochemical and biochemical processes
Keywords
olvanil, vanilloid receptor, CB1 receptor, CB2 receptor, acyl chain length, cis double bonds, omega-6 fatty acids, omega-3 fatty acids, breast cancer cell proliferation
MeSH terms
Fatty Acid Amide Hydrolases, Amidohydrolases, Animals, Arachidonic Acids, Binding Sites, Biological Transport, Capsaicin, Cell Division, Cell Line, Cell Membrane, Diffusion, Electric Conductivity, Fatty Acids, Unsaturated, Humans, Ligands, Oocytes, Receptors, Drug, Xenopus laevis, Receptors, Cannabinoid, Receptor, Cannabinoid, CB2, Mice, Rats, Polyunsaturated Alkamides, Endocannabinoids

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