2003
DOI: 10.1074/jbc.m307258200
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G Protein-coupled Endothelial Receptor for Atypical Cannabinoid Ligands Modulates a Ca2+-dependent K+ Current

Abstract: The cannabinoid analog "abnormal cannabidiol" (abn-cbd) causes endothelium-dependent vasodilation in rat isolated mesenteric arteries through a G protein-coupled receptor distinct from CB 1 or CB 2 . We examined the actions of abn-cbd on the electrophysiology of human umbilical vein endothelial cells (HU-VEC), using the whole cell version of the patch clamp technique. Voltage steps produced noninactivating outward currents, which were abolished by iberiotoxin or by chelation of intracellular calcium. The prese… Show more

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Cited by 86 publications
(93 citation statements)
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“…Two cannabinoid G protein-coupled receptors have been cloned thus far, CB 1 receptors (Matsuda et al, 1990), expressed primarily by neurons, and CB 2 receptors (Munro et al, 1993), expressed primarily by immune cells. Aside from these two receptors, evidence exists supporting the presence of yet uncloned cannabinoid receptors, a hypothesis predominantly based on pharmacological activity of cannabinoid compounds in CB 1 and CB 2 receptor-deficient mice or following the administration of 'selective' CB 1 and CB 2 receptor antagonists (Jarai et al, 1999;Di Marzo et al, 2000;Breivogel et al, 2001;Hajos & Freund, 2002;Begg et al, 2003). Here cannabinoids are defined as ingredients of the cannabis plant or other compounds that bind to and activate cannabinoid receptors, and Table 1 summarizes their pharmacological properties.…”
Section: Introductionmentioning
confidence: 99%
“…Two cannabinoid G protein-coupled receptors have been cloned thus far, CB 1 receptors (Matsuda et al, 1990), expressed primarily by neurons, and CB 2 receptors (Munro et al, 1993), expressed primarily by immune cells. Aside from these two receptors, evidence exists supporting the presence of yet uncloned cannabinoid receptors, a hypothesis predominantly based on pharmacological activity of cannabinoid compounds in CB 1 and CB 2 receptor-deficient mice or following the administration of 'selective' CB 1 and CB 2 receptor antagonists (Jarai et al, 1999;Di Marzo et al, 2000;Breivogel et al, 2001;Hajos & Freund, 2002;Begg et al, 2003). Here cannabinoids are defined as ingredients of the cannabis plant or other compounds that bind to and activate cannabinoid receptors, and Table 1 summarizes their pharmacological properties.…”
Section: Introductionmentioning
confidence: 99%
“…99 Several lines of evidence suggest that endothelial cells express this novel cannabinoid receptor, and its activation leads to the release of nitric oxide, culminating in the opening of potassium channels on vascular smooth muscle and leading to relaxation and vasodilation. 100 Although there are strong pharmacological parallels between the vascular and hippocampal novel receptors, there are some notable differences. For example, the vascular receptor is insensitive to potent synthetic cannabinoids.…”
Section: Non-cb1/cb2 Receptors In the Vasculaturementioning
confidence: 99%
“…This receptor exhibited a high affinity to the regioisomer of cannabidiol, abnormal cannabidiol. 19,20 This receptor promoted endothelium-dependent vasodilation of isolated rat mesenteric arteries via opening of Ca 2+ -dependent K + channel. 19,20 19 It has been also established that in endothelial cells abnormal cannabidiol activates extracellular signal-regulated kinase (ERK) and Akt kinase.…”
Section: A Brief History Of the Discovery Of Endogenous Cannabinoid Smentioning
confidence: 99%
“…19,20 This receptor promoted endothelium-dependent vasodilation of isolated rat mesenteric arteries via opening of Ca 2+ -dependent K + channel. 19,20 19 It has been also established that in endothelial cells abnormal cannabidiol activates extracellular signal-regulated kinase (ERK) and Akt kinase. 20 Abnormal cannabidiol-induced vasorelaxation was maintained after inhibition of NO-synthase by L-NAME or in combination with vanilloid VR1 receptor antagonist capsazepine.…”
Section: A Brief History Of the Discovery Of Endogenous Cannabinoid Smentioning
confidence: 99%