Premium
The effects of Δ 9 ‐tetrahydrocannabinol in rat mesenteric vasculature, and its interactions with the endocannabinoid anandamide
Author(s) -
O'Sullivan Saoirse E,
Kendall David A,
Randall Michael D
Publication year - 2005
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706218
Subject(s) - capsazepine , chemistry , apamin , am251 , agonist , trpv1 , pharmacology , anandamide , cannabinoid , cannabinoid receptor , glibenclamide , charybdotoxin , endocrinology , medicine , receptor , biochemistry , calcium , membrane potential , transient receptor potential channel , organic chemistry , diabetes mellitus
1 Δ 9 ‐tetrahydrocannabinol (THC) produces varying effects in mesenteric arteries: vasorelaxation (third‐order branches, G3), modest vasorelaxation (G2), no effect (G1) and vasoconstriction (the superior mesenteric artery, G0). 2 In G3, vasorelaxation to THC was inhibited by pertussis toxin, but was unaffected by the CB 1 receptor antagonist, AM251 (1 μ M ), incubation with the TRPV1 receptor agonist capsaicin (10 μ M , 1 h), the TRPV1 receptor antagonist capsazepine (10 μ M ) or de‐endothelialisation. 3 In G3, vasorelaxation to THC was inhibited by high K + buffer, and by the following K + channel inhibitors: charybdotoxin (100 n M ), apamin (500 n M ) and barium chloride (30 μ M ), but not by 4‐aminopyridine, glibenclamide or tertiapin. 4 In G3, THC (10 and 100 μ M ) inhibited the contractile response to Ca 2+ in a Ca 2+ ‐free, high potassium buffer, indicating that THC blocks Ca 2+ influx. 5 In G0, the vasoconstrictor responses to THC were inhibited by de‐endothelialisation and SR141716A (100 n M ), but not by the endothelin (ET A ) receptor antagonist FR139317 (1 μ M ). 6 THC (1 and 10 μ M ) antagonised vasorelaxation to anandamide in G3 but not G0. THC did not antagonise the noncannabinoid verapamil, capsaicin or the CB 1 receptor agonist CP55,940. THC (10 and 100 μ M ) inhibited endothelium‐derived relaxing factor (EDHF)‐mediated responses to carbachol in a manner similar to the gap junction inhibitor 18 α ‐glycyrrhetinic acid. 7 These data show that THC causes vasorelaxation through activation of K + channels and inhibition of Ca 2+ channels, and this involves non‐CB 1 , non‐TRPV1 but G‐protein‐coupled receptors. In G0, THC does not cause relaxation and at high concentrations causes contractions. Importantly, THC antagonises the effects of anandamide, possibly through inhibition of EDHF activity.British Journal of Pharmacology (2005) 145 , 514–526. doi: 10.1038/sj.bjp.0706218