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Aim: Plant cannabinoids, like [DELTA]9-tetrahydrocannabinol (THC) and cannabidiol (CBD), activate/desensitize thermosensitive transient receptor potential (TRP) channels of vanilloid type-1 or -2 (TRPV1 or TRPV2). We investigated whether cannabinoids also activate/desensitize two other 'thermo-TRP's', the TRP channels of vanilloid type-3 or -4 (TRPV3 or TRPV4), and if the TRPV-inactive cannabichromene (CBC) modifies the expression of TRPV1-4 channels in the gastrointestinal tract.

Methods: TRP activity was assessed by evaluating elevation of [Ca2 ]i in rat recombinant TRPV3- and TRPV4-expressing HEK-293 cells. TRP channel mRNA expression was measured by quantitative RT-PCR in the jejunum and ileum of mice treated with vehicle or the pro-inflammatory agent croton oil.

Results: (i) CBD and tetrahydrocannabivarin (THCV) stimulated TRPV3-mediated [Ca2 ]i with high efficacy (50-70% of the effect of ionomycin) and potency (EC50~3.7 [mu]m), whereas cannabigerovarin (CBGV) and cannabigerolic acid (CBGA) were significantly more efficacious at desensitizing this channel to the action of carvacrol than at activating it; (ii) cannabidivarin and THCV stimulated TRPV4-mediated [Ca2 ]i with moderate-high efficacy (30-60% of the effect of ionomycin) and potency (EC50 0.9-6.4 [mu]m), whereas CBGA, CBGV, cannabinol and cannabigerol were significantly more efficacious at desensitizing this channel to the action of 4-[alpha]-phorbol 12,13-didecanoate (4[alpha]-PDD) than at activating it; (iii) CBC reduced TRPV1[beta], TRPV3 and TRPV4 mRNA in the jejunum, and TRPV3 and TRPV4 mRNA in the ileum of croton oil-treated mice.

Conclusions: Cannabinoids can affect both the activity and the expression of TRPV1-4 channels, with various potential therapeutic applications, including in the gastrointestinal tract.

Copyright (C) 2012 Blackwell Publishing Ltd.