Samson and colleagues elegantly demonstrated the coexpression of CB1/CB2 receptors in a mast cell line (RBL2H3) and noted that while CB1 was functional in the suppression of serotonin release, CB2 was the predominant mediator of cannabinoid-induced AKT and ERK kinase phosphorylation (1). We recently reported that L-NAME, an inhibitor of NO synthase (NOS), prevented the inhibitory effect of exogenous (CP 55,940) and endogenous (2-arachidonylglycerol) cannabinoids on the Ag-induced activation of guinea-pig mast cells (2). The effect of cannabinoids was reasonably CB2 mediated, since it was completely reverted by a selective CB2 receptor antagonist (SR144528) (2, 3). CP 55,940 and 2-arachidonylglycerol increased the production of nitrites and cGMP, measured in guinea-pig mast cells supernatants, and promoted the intracellular expression of the inducible isoform of NOS (iNOS), as shown through a Western blot analysis (manuscript in preparation). Since NO involvement in AKT and ERK activation has been shown in several cell types (4, 5), we wonder whether the cannabinoid-induced phosphorylation of AKT and ERK kinases, clearly showed by Samson et al., may occur via a NO/cGMP dependent pathway. In our opinion, a set of experiments performed in the presence or in the absence of inhibitors of NO and cGMP generation may be of interest in the understanding of the multiple transcriptional events induced by cannabinoid exposure.
- Copyright © 2003 by The American Association of Immunologists