Interactions between synthetic vanilloids and the endogenous cannabinoid system

V Di Marzo, T Bisogno, D Melck, Ruth Alexandra Ross, H Brockie, Lesley Ann Stevenson, Roger Guy Pertwee, L De Petrocellis

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141 Citations (Scopus)


The chemical similarity between some synthetic agonists of vanilloid receptors, such as olvanil (N-vanillyl-cis-9-octadecenoamide), and the 'endocannabinoid' anandamide (arachidonoyl-ethanolamide, AEA), suggests possible interactions between the cannabinoid and vanilloid signalling systems. Here we report that olvanil is a stable and potent inhibitor of AEA facilitated transport into rat basophilic leukemia (RBL-2H3) cells, Olvanil blocked both the uptake and the hydrolysis of [C-14]AEA by intact RBL-2H3 cells (IC50=9 mu M), while capsaicin and pseudocapsaicin (N-vanillyl-nonanamide) were much less active. Olvanil was more potent than previously reported inhibitors of AEA facilitated transport, i,e; phloretin (IC50=80 mu M), AM404 (12.9% inhibition at 10 mu M) or oleoylethamolamide (27.5% inhibition at 10 mu M) Olvanil was a poor inhibitor of [C-14]AEA hydrolysis by RBL-2H3 and N18TG2 cell membranes, suggesting that the inhibitory effect on [C-14]AEA breakdown observed in intact cells vr,as due to inhibition of [C-14]AEA uptake. Olvanil was stable to enzymatic hydrolysis, and (i) displaced the binding of high affinity cannabinoid receptor ligands to membrane preparations from N18TG2 cells and guinea pig forebrain (K-i = 1.64-7.08 mu M), but not from cells expressing the CB2 cannabinoid receptor subtype; (ii) inhibited forskolin-induced cAMP formation in intact N18TG2 cells (IC50 = 1.60 mu M), this effect being reversed by the selective CB1 antagonist SR141716A. Pseudocapsaicin, but not capsaicin, also selectively bound to CB1 receptor-containing membranes. These data suggest that some of the analgesic actions of olvanil may be due to its interactions with the endogenous cannabinoid system, and may lead to the design of a novel class of cannabimimetics with potential therapeutic applications as analgesics. (C) 1998 Federation of European Biochemical Societies.

Original languageEnglish
Pages (from-to)449-454
Number of pages6
JournalFEBS Letters
Issue number3
Publication statusPublished - 9 Oct 1998


  • vanilloid receptor
  • cannabinoid receptor
  • endocannabinoid
  • anandamide
  • capsaicin
  • inflammation
  • antinociception
  • mast cell
  • NE-19550
  • vanilloid receptor
  • cannabinoid receptor;
  • inflammation


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