title: Mechanisms of vasorelaxation induced by the cannabidiol analogue compound O-1602 in the rat small mesenteric artery.
abstract: Atypical cannabinoid O-1602 (5-Methyl-4-[(1R,6R)-3-methyl-6-(1-cyclohexen-1-yl]-1,3-benzenediol) induces vasorelaxation and activates the orphan G protein-coupled receptor GPR55 in human endothelial cells. This study investigates the underlying mechanisms of vasorelaxation induced by this compound. The vasodilator activity was assessed in the rat third order branch of the superior mesenteric artery using a wire myograph. The vasorelaxation was partially endothelium-dependent (pEC50%=5.8±0.3). The endothelial component was antagonized by the putative endothelial receptor antagonists rimonabant (3 µM; pEC50%=5.1±0.2) and O-1918 (10 µM; pEC50%=5.3±0.2) but not by the CB1 and CB2 receptors antagonists AM 251 (10 µM) and AM 630 (10 µM), respectively. The vasorelaxation was not pertussis toxin-sensitive and not mediated through TRPVI receptors or by the release of NO, but was reduced by inhibition of Ca2+ sensitive K+ channels (KCa). In endothelium-denuded vessels, O-1602 abolished CaCl2-induced contraction and the inhibition was apparently reversed by O-1918. O-1602 mediates its vasorelaxant effects partly by an endothelium-dependent pathway involving rimonabant- and O-1918-sensitive targets that are distinct from the classical CB1 and CB2 cannabinoid receptors and might involve activation of KCa. The endothelium-independent relaxation might involve interfering with Ca2+ entry.
authors: Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, 35, Alkoudh 123, Oman. Electronic address: yousufm@squ.edu.om.
authors: Y M
authors: YM
authors: Al Suleimani
authors: Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, 35, Alkoudh 123, Oman.
authors: A S
authors: AS
authors: Al Mahruqi
authors: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1 PD, UK.
authors: C R
authors: CR
authors: Hiley
mesh_terms: D000818:Animals; D002185:Cannabidiol / Q000378:metabolism / Q000494:pharmacology* / Q000031:analogs & derivatives; D003510:Cyclohexanes / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012118:Resorcinols / Q000378:metabolism / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D003510:Cyclohexanes; D012118:Resorcinols; D002185:Cannabidiol; C568537:O-1602 compound
keywords: Ca(2+) sensitive K(+) channels; Cannabinoid receptor; Endothelium; O-1602; Vasorelaxation