Cannabinoid actions at TRPV channels

effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation

L De Petrocellis, P Orlando, A Schiano Moriello, G Aviello, C Stott, A A Izzo, V Di Marzo

Research output: Contribution to journalArticle

112 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)255-266
Number of pages12
JournalActa Physiologica
Volume204
Issue number2
Early online date12 Aug 2011
DOIs
Publication statusPublished - Feb 2012

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Transient Receptor Potential Channels
Cannabinoids
Croton Oil
Cannabidiol
Ionomycin
Jejunum
Inflammation
Ileum
Messenger RNA
Gastrointestinal Tract
Cannabinol
Dronabinol
HEK293 Cells
Polymerase Chain Reaction
cannabichromene
cannabigerolic acid
Therapeutics

Keywords

  • Animals
  • Calcium
  • Cannabidiol
  • Cannabinoids
  • Dronabinol
  • Gastrointestinal Diseases
  • HEK293 Cells
  • Humans
  • Inflammation
  • Intestine, Small
  • Mice
  • Rats
  • TRPV Cation Channels
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

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, 204(2), 255-266. https://doi.org/10.1111/j.1748-1716.2011.02338.x

Cannabinoid actions at TRPV channels : effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation. / De Petrocellis, L; Orlando, P; Moriello, A Schiano; Aviello, G; Stott, C; Izzo, A A; Di Marzo, V.

In: Acta Physiologica, Vol. 204, No. 2, 02.2012, p. 255-266.

Research output: Contribution to journalArticle

De Petrocellis, L, Orlando, P, Moriello, AS, Aviello, G, Stott, C, Izzo, AA & Di Marzo, V 2012, 'Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation', Acta Physiologica, vol. 204, no. 2, pp. 255-266. https://doi.org/10.1111/j.1748-1716.2011.02338.x
De Petrocellis, L ; Orlando, P ; Moriello, A Schiano ; Aviello, G ; Stott, C ; Izzo, A A ; Di Marzo, V. / Cannabinoid actions at TRPV channels : effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation. In: Acta Physiologica. 2012 ; Vol. 204, No. 2. pp. 255-266.
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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.",
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T2 - 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

N1 - © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.

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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.

AB - 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.

KW - Animals

KW - Calcium

KW - Cannabidiol

KW - Cannabinoids

KW - Dronabinol

KW - Gastrointestinal Diseases

KW - HEK293 Cells

KW - Humans

KW - Inflammation

KW - Intestine, Small

KW - Mice

KW - Rats

KW - TRPV Cation Channels

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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DO - 10.1111/j.1748-1716.2011.02338.x

M3 - Article

VL - 204

SP - 255

EP - 266

JO - Acta Physiologica

JF - Acta Physiologica

SN - 1748-1708

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ER -