Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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A more recent version of this article appeared on June 1, 2007

Published online before print March 5, 2007
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1206738

Received for publication December 20, 2006.
Revised January 26, 2007.
Accepted for publication February 5, 2007.

Article

Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL-2H3 mast cells

Elda Del Giudice *, Luciano Rinaldi *, Marzia Passarotto *, Fabrizio Facchinetti *, Antonello D’Arrigo *, Adriano Guiotto {dagger}, Maurizio Dalle Carbonare *, Leontino Battistin {ddagger}, and Alberta Leon *{ddagger}@

*Research and Innovation (R&I) Company, Padova, Italy; {dagger}Department of Pharmaceutical Sciences, University of Padova, Padova, Italy; and {ddagger}San Camillo Hospital, IRCCS, Venezia-Lido, Italy

@ To whom correspondence should be addressed. E-mail: albertaleon{at}researchinnovation.com.


  Abstract

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 (3-10 µM) augments {beta}-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 (10-30 µM). This action, although mimicked by {Delta}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 V1, did not affect [Ca2+]i levels 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: {beta}-hexosaminidase • calcium • ion channels • {Delta}9-tetrahydrocannabinol • CB receptors • VR1 receptors • TRP channels






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Copyright © 2007 by the Society for Leukocyte Biology.