Human platelets bind and degrade 2-arachidonoylglycerol, which activates these cells through a cannabinoid receptor

Mauro Maccarrone, Monica Bari, Adriana Menichelli, Elena Giuliani, Domenico Del Principe, Alessandro Finazzi-Agrò

Research output: Contribution to journalArticlepeer-review


The endocannabinoid 2-arachidonoylglycerol (2-Δ4Ach-Gro) activates human platelets in platelet-rich plasma at physiological concentrations. The activation was inhibited by selective antagonists of CB1 and CB2 cannabinoid receptors, but not by acetylsalicylic acid. Human platelets can metabolize 2-Δ4Ach-Gro by internalization through a high affinity transporter (Km = 300 ± 30 nM, Vmax = 10 ± 1 pmol·min-1·mg protein-1), followed by hydrolysis by a fatty acid amide hydrolase (Km = 8 ± 1 μM, Vmax = 400 ± 50 pmol·min-1·mg protein-1). The anandamide transport inhibitor AM404, and anandamide itself, were ineffective on 2-Δ4Ach-Gro uptake by platelets, whereas anandamide competitively inhibited 2-Δ4Ach-Gro hydrolysis (inhibition constant = 10 ± 1 μM). Platelet activation by 2-Δ4Ach-Gro was paralleled by an increase of intracellular calcium and inositol-1,4,5-trisphosphate, and by a decrease of cyclic AMP. Moreover, treatment of preloaded platelet-rich plasma with 2-Δ4Ach-Gro induced an approximately threefold increase in [3H]2-Δ4Ach-Gro release, according to a CB receptor-dependent mechanism. On the other hand, ADP and collagen counteracted the activation of platelets by 2-Δ4Ach-Gro, whereas 5-hydroxytryptamine (serotonin) enhanced and extended its effects. Remarkably, ADP and collagen also reduced [3H]2-Δ4Ach-Gro release from 2-Δ4Ach-Gro-activated platelets, whereas 5-hydroxytryptamine further increased it. These findings suggest a so far unnoticed interplay between the peripheral endocannabinoid system and physiological platelet agonists.

Original languageEnglish
Pages (from-to)819-825
Number of pages7
JournalEuropean Journal of Biochemistry
Issue number3
Publication statusPublished - 2001


  • 2-arachidonoylglycerol
  • 5-hydroxytryptamine (serotonin)
  • ADP
  • Cannabinoid receptors
  • Platelet

ASJC Scopus subject areas

  • Biochemistry


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