Plant-Derived Cannabinoids Modulate the Activity of Transient Receptor Potential Channels of Ankyrin Type-1 and Melastatin Type-8
| Autor: | Vittorio Vellani, Pietro Marini, Vincenzo Di Marzo, Pierangelo Orlando, Pier Cosimo Magherini, Luciano De Petrocellis, Aniello Schiano-Moriello |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
TRPM8
Ankyrins Cannabigerol TRPV1 TRPM Cation Channels ION-CHANNEL Pharmacology Transfection TRPA1 TRP CHANNELS Cell Line Rats Sprague-Dawley Transient receptor potential channel chemistry.chemical_compound Cannabichromene endocannabinoids pain hyperalgesia Ganglia Spinal medicine Animals Humans TRPA1 Cation Channel Cells Cultured Cannabis TRPC Cation Channels Neurons Cannabinoids Icilin Endocannabinoid system PROSTATE-CANCER Rats chemistry SENSORY NEURONS Molecular Medicine Calcium Calcium Channels NOCICEPTIVE NEURONS Cannabidiol medicine.drug |
| Zdroj: | 325 (2008): 1007–1015. info:cnr-pdr/source/autori:De Petrocellis L, Vellani V, Schiano-Moriello A, Marini P, Magherini PC, Orlando P, Di Marzo V./titolo:Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8./doi:/rivista:/anno:2008/pagina_da:1007/pagina_a:1015/intervallo_pagine:1007–1015/volume:325 The Journal of pharmacology and experimental therapeutics 325 (2008): 1007–1015. doi:10.1124/jpet.107.134809 info:cnr-pdr/source/autori:De Petrocellis L, Vellani V, Schiano-Moriello A, Marini P, Magherini PC, Orlando P, Di Marzo V./titolo:Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8./doi:10.1124%2Fjpet.107.134809/rivista:The Journal of pharmacology and experimental therapeutics (Print)/anno:2008/pagina_da:1007/pagina_a:1015/intervallo_pagine:1007–1015/volume:325 |
| ISSN: | 1521-0103 0022-3565 |
| DOI: | 10.1124/jpet.107.134809 |
| Popis: | The plant cannabinoids (phytocannabinoids), cannabidiol (CBD), and Delta(9)-tetrahydrocannabinol (THC) were previously shown to activate transient receptor potential channels of both vanilloid type 1 (TRPV1) and ankyrin type 1 (TRPA1), respectively. Furthermore, the endocannabinoid anandamide is known to activate TRPV1 and was recently found to antagonize the menthol- and icilin-sensitive transient receptor potential channels of melastatin type 8 (TRPM8). In this study, we investigated the effects of six phytocannabinoids [i.e., CBD, THC, CBD acid, THC acid, cannabichromene (CBC), and cannabigerol (CBG)] on TRPA1- and TRPM8-mediated increase in intracellular Ca2+ in either HEK-293 cells overexpressing the two channels or rat dorsal root ganglia (DRG) sensory neurons. All of the compounds tested induced TRPA1-mediated Ca2+ elevation in HEK-293 cells with efficacy comparable with that of mustard oil isothiocyanates (MO), the most potent being CBC (EC(50) = 60 nM) and the least potent being CBG and CBD acid (EC(50) = 3.4-12.0 microM). CBC also activated MO-sensitive DRG neurons, although with lower potency (EC(50) = 34.3 microM). Furthermore, although none of the compounds tested activated TRPM8-mediated Ca2+ elevation in HEK-293 cells, they all, with the exception of CBC, antagonized this response when it was induced by either menthol or icilin. CBD, CBG, THC, and THC acid were equipotent (IC(50) = 70-160 nM), whereas CBD acid was the least potent compound (IC(50) = 0.9-1.6 microM). CBG inhibited Ca2+ elevation also in icilin-sensitive DRG neurons with potency (IC(50) = 4.5 microM) similar to that of anandamide (IC(50) = 10 microM). Our findings suggest that phytocannabinoids and cannabis extracts exert some of their pharmacological actions also by interacting with TRPA1 and TRPM8 channels, with potential implications for the treatment of pain and cancer. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|