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Published online before print March 5, 2007
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,1
* Research and Innovation (R&I) Company, Padova, Italy;
Department of Pharmaceutical Sciences, University of Padova, Padova, Italy; and
San Camillo Hospital, IRCCS, Venezia-Lido, Italy
1 Correspondence: Research and Innovation (R&I) Company, Via Svizzera 16, 35127 Padova, Italy. E-mail: albertaleon{at}researchinnovation.com
Cannabidiol (CBD), a prominent psychoinactive component of cannabis with negligible affinity for known cannabinoid receptors, exerts numerous pharmacological actions, including anti-inflammatory and immunosuppressive effects, the underlying mechanisms of which remain unclear. In the current study, we questioned whether CBD modulates activation of mast cells, key players in inflammation. By using the rat basophilic leukemia mast cell line (RBL-2H3), we demonstrate that CBD (310 µM) augments ß-hexosaminidase release, a marker of cell activation, from antigen-stimulated and unstimulated cells via a mechanism, which is not mediated by Gi/Go protein-coupled receptors but rather is associated with a robust rise in intracellular calcium ([Ca2+]i) levels sensitive to clotrimazole and nitrendipine (1030 µM). This action, although mimicked by
9-tetrahydrocannabinol (THC), is opposite to that inhibitory, exerted by the synthetic cannabinoids WIN 55,212-2 and CP 55,940. Moreover, the vanilloid capsaicin, a full agonist of transient receptor potential channel VR1, did not affect [Ca2+]ilevels in the RBL-2H3 cells, thus excluding the involvement of this receptor in the CBD-mediated effects. Together, these results support existence of yet-to-be identified sites of interaction, i.e., receptors and/or ion channels associated with Ca2+ influx of natural cannabinoids such as CBD and THC, the identification of which has the potential to provide for novel strategies and agents of therapeutic interest.
Key Words: ß-hexosaminidase calcium ion channels
9-tetrahydrocannabinol CB receptors VR1 receptors TRP channels
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