title: Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation.
abstract: OBJECTIVE
  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: Endocannabinoid Research Group, Institute of Cybernetics, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy.
authors: L
authors: L
authors: De Petrocellis
authors: P
authors: P
authors: Orlando
authors: A Schiano
authors: AS
authors: Moriello
authors: G
authors: G
authors: Aviello
authors: C
authors: C
authors: Stott
authors: A A
authors: AA
authors: Izzo
authors: V
authors: V
authors: Di Marzo
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002185:Cannabidiol / Q000737:chemistry / Q000494:pharmacology; D002186:Cannabinoids / Q000737:chemistry / Q000494:pharmacology*; D013759:Dronabinol / Q000737:chemistry / Q000494:pharmacology; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism*; D051379:Mice; D051381:Rats; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D002186:Cannabinoids; D050916:TRPV Cation Channels; C505767:TRPV3 protein, rat; C486760:Trpv3 protein, mouse; C486576:Trpv4 protein, mouse; C486577:Trpv4 protein, rat; D002185:Cannabidiol; D013759:Dronabinol; C037036:cannabigerol; C010695:cannabichromene; D002118:Calcium