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Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation.
Acta Physiol (Oxf) 2012; 204(2):255-66AP

Abstract

AIM

Plant cannabinoids, like Δ(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 [Ca(2+)](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 [Ca(2+)](i) with high efficacy (50-70% of the effect of ionomycin) and potency (EC(50∼) 3.7 μm), 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 [Ca(2+)](i) with moderate-high efficacy (30-60% of the effect of ionomycin) and potency (EC(50) 0.9-6.4 μm), whereas CBGA, CBGV, cannabinol and cannabigerol were significantly more efficacious at desensitizing this channel to the action of 4-α-phorbol 12,13-didecanoate (4α-PDD) than at activating it; (iii) CBC reduced TRPV1β, 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.

Authors+Show Affiliations

Endocannabinoid Research Group, Institute of Cybernetics, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21726418

Citation

De Petrocellis, L, et al. "Cannabinoid Actions at TRPV Channels: Effects On TRPV3 and TRPV4 and Their Potential Relevance to Gastrointestinal Inflammation." Acta Physiologica (Oxford, England), vol. 204, no. 2, 2012, pp. 255-66.
De Petrocellis L, Orlando P, Moriello AS, et al. Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation. Acta Physiol (Oxf). 2012;204(2):255-66.
De Petrocellis, L., Orlando, P., Moriello, A. S., Aviello, G., Stott, C., Izzo, A. A., & Di Marzo, V. (2012). Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation. Acta Physiologica (Oxford, England), 204(2), pp. 255-66. doi:10.1111/j.1748-1716.2011.02338.x.
De Petrocellis L, et al. Cannabinoid Actions at TRPV Channels: Effects On TRPV3 and TRPV4 and Their Potential Relevance to Gastrointestinal Inflammation. Acta Physiol (Oxf). 2012;204(2):255-66. PubMed PMID: 21726418.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation. AU - De Petrocellis,L, AU - Orlando,P, AU - Moriello,A Schiano, AU - Aviello,G, AU - Stott,C, AU - Izzo,A A, AU - Di Marzo,V, Y1 - 2011/08/12/ PY - 2011/7/6/entrez PY - 2011/7/6/pubmed PY - 2012/5/9/medline SP - 255 EP - 66 JF - Acta physiologica (Oxford, England) JO - Acta Physiol (Oxf) VL - 204 IS - 2 N2 - AIM: Plant cannabinoids, like Δ(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 [Ca(2+)](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 [Ca(2+)](i) with high efficacy (50-70% of the effect of ionomycin) and potency (EC(50∼) 3.7 μm), 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 [Ca(2+)](i) with moderate-high efficacy (30-60% of the effect of ionomycin) and potency (EC(50) 0.9-6.4 μm), whereas CBGA, CBGV, cannabinol and cannabigerol were significantly more efficacious at desensitizing this channel to the action of 4-α-phorbol 12,13-didecanoate (4α-PDD) than at activating it; (iii) CBC reduced TRPV1β, 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. SN - 1748-1716 UR - https://www.unboundmedicine.com/medline/citation/21726418/Cannabinoid_actions_at_TRPV_channels:_effects_on_TRPV3_and_TRPV4_and_their_potential_relevance_to_gastrointestinal_inflammation_ L2 - https://doi.org/10.1111/j.1748-1716.2011.02338.x DB - PRIME DP - Unbound Medicine ER -