Cannabinomimetic behavioral effects of and adenylate cyclase inhibition by two new endogenous anandamides

Jacob Barg, Ester Fride, Lumir Hanus, Rivka Levy, Noa Matus-Leibovitch, Eliahu Heldman, Michael Bayewitch, Raphael Mechoulam, Zvi Vogel

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


We have previously shown that the endogenous putative cannabinoid ligand arachidonylethanolamide (anandamide, 20:4, n - 6) induces in vivo and in vitro effects typical of a cannabinoid agonist. We now report that two other endogenous anandamides, docosatetraenylethanolamide (anandamide, 22:4, n - 6) and homo-γ-linolenylethanolamide (anandamide, 20:3, n - 6), have similar activities. The new anandamides bind to SV40-transformed African green monkey kidney cells transfected with the rat brain cannabinoid receptor cDNA and display KI values of 253.4 ± 41.1 and 244.8 ± 38.7, respectively. The value found for arachidonylethanolamide was 155.1 ± 13.8 nM. In addition, the new anandamides inhibit prostaglandin E1-stimulated adenylate cyclase activity in Chinese hamster ovary-K1 cells transfected with the cannabinoid receptor, as well as in N18TG2 mouse neuroblastoma cells that express the cannabinoid receptor naturally. The IC50 values for the inhibition of adenylate cyclase in transfected Chinese hamster ovary-K1 cells were 116.8 ± 8.7 and 109.3 ± 8.6 nM for docosatetraenylethanolamide and homo-γ-linolenylethanolamide, respectively. These values were similar to that obtained with arachidonylethanolamide (100.5 ± 7.7 nM), but were significantly higher than the IC50 value observed with the plant cannabinoid Δ9-tetrahydrocannabinol (9.2 ± 8.6 nM). The inhibitory effects of the anandamides on adenylate cyclase activity were blocked by pertussis toxin, indicating the involvement of pertussis toxin-sensitive GTP-binding protein(s). In a tetrad of behavioral assays for cannabinoid-like effects, the two new anandamides exerted similar behavioral effects to those observed with Δ9-tetrahydrocannabinol and arachidonylethanolamide: inhibition of motor activity in an open field, hypothermia, catalepsy on a ring, and analgesia on a hot plate.

Original languageEnglish
Pages (from-to)145-152
Number of pages8
JournalEuropean Journal of Pharmacology
Issue number2
StatePublished - 12 Dec 1995
Externally publishedYes


  • Adenylate cyclase
  • Anandamide
  • Cannabinoid receptor
  • GTP-binding protein

ASJC Scopus subject areas

  • Pharmacology


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