共 40 条
Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8
被引:243
作者:

De Petrocellis, Luciano
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机构:
CNR, Endocannabinoid Res Grp, Inst Biomol Chem, I-80078 Pozzuoli, NA, Italy
CNR, Inst Cybernet, I-80078 Pozzuoli, NA, Italy CNR, Endocannabinoid Res Grp, Inst Biomol Chem, I-80078 Pozzuoli, NA, Italy

Vellani, Vittorio
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机构:
Univ Modena, Dept Biomed Sci, I-41100 Modena, Italy CNR, Endocannabinoid Res Grp, Inst Biomol Chem, I-80078 Pozzuoli, NA, Italy

Schiano-Moriello, Aniello
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机构:
CNR, Endocannabinoid Res Grp, Inst Biomol Chem, I-80078 Pozzuoli, NA, Italy
CNR, Inst Cybernet, I-80078 Pozzuoli, NA, Italy CNR, Endocannabinoid Res Grp, Inst Biomol Chem, I-80078 Pozzuoli, NA, Italy

Marini, Pietro
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CNR, Endocannabinoid Res Grp, Inst Biomol Chem, I-80078 Pozzuoli, NA, Italy CNR, Endocannabinoid Res Grp, Inst Biomol Chem, I-80078 Pozzuoli, NA, Italy

Magherini, Pier Cosimo
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机构:
CNR, Endocannabinoid Res Grp, Inst Biomol Chem, I-80078 Pozzuoli, NA, Italy
Univ Modena, Dept Biomed Sci, I-41100 Modena, Italy CNR, Endocannabinoid Res Grp, Inst Biomol Chem, I-80078 Pozzuoli, NA, Italy

Orlando, Pierangelo
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h-index: 0
机构:
CNR, Endocannabinoid Res Grp, Inst Biomol Chem, I-80078 Pozzuoli, NA, Italy
CNR, Inst Prot Biochem, I-80078 Pozzuoli, NA, Italy CNR, Endocannabinoid Res Grp, Inst Biomol Chem, I-80078 Pozzuoli, NA, Italy

Di Marzo, Vincenzo
论文数: 0 引用数: 0
h-index: 0
机构:
CNR, Endocannabinoid Res Grp, Inst Biomol Chem, I-80078 Pozzuoli, NA, Italy CNR, Endocannabinoid Res Grp, Inst Biomol Chem, I-80078 Pozzuoli, NA, Italy
机构:
[1] CNR, Endocannabinoid Res Grp, Inst Biomol Chem, I-80078 Pozzuoli, NA, Italy
[2] CNR, Inst Cybernet, I-80078 Pozzuoli, NA, Italy
[3] CNR, Inst Prot Biochem, I-80078 Pozzuoli, NA, Italy
[4] Univ Modena, Dept Biomed Sci, I-41100 Modena, Italy
关键词:
D O I:
10.1124/jpet.107.134809
中图分类号:
R9 [药学];
学科分类号:
1007 ;
摘要:
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 EC50 = 60 nM) and the least potent being CBG and CBD acid (EC50 = 3.4-12.0 mu M). CBC also activated MO-sensitive DRG neurons, although with lower potency (EC50 = 34.3 mu M). 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 (IC50 = 70-160 nM), whereas CBD acid was the least potent compound (IC50 = 0.9-1.6 mu M). CBG inhibited Ca2+ elevation also in icilin-sensitive DRG neurons with potency (IC50 = 4.5 mu M) similar to that of anandamide (IC50 = 10 mu M). 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.
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页码:1007 / 1015
页数:9
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