Mechanisms of vasorelaxation induced by the cannabidiol analogue compound O-1602 in the rat small mesenteric artery

Y. M. Al Suleimani, A. S. Al Mahruqi, C. R. Hiley

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Article number70169
Pages (from-to)107-114
Number of pages8
JournalEuropean Journal of Pharmacology
Volume765
DOIs
Publication statusPublished - Aug 18 2015

Fingerprint

Cannabidiol
rimonabant
Mesenteric Arteries
Vasodilation
Endothelium
Cannabinoid Receptor CB2
Cannabinoid Receptor CB1
Vasodilator Agents
Superior Mesenteric Artery
Cannabinoids
Pertussis Toxin
G-Protein-Coupled Receptors
Endothelial Cells
O-1602 compound
O 1602

Keywords

  • Ca<sup>2+</sup> sensitive K<sup>+</sup> channels
  • Cannabinoid receptor
  • Endothelium
  • O-1602
  • Vasorelaxation

ASJC Scopus subject areas

  • Pharmacology

Cite this

Mechanisms of vasorelaxation induced by the cannabidiol analogue compound O-1602 in the rat small mesenteric artery. / Al Suleimani, Y. M.; Al Mahruqi, A. S.; Hiley, C. R.

In: European Journal of Pharmacology, Vol. 765, 70169, 18.08.2015, p. 107-114.

Research output: Contribution to journalArticle

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