The quest for endothelial atypical cannabinoid receptor: BKCa channels act as cellular sensors for cannabinoids in in vitro and in situ endothelial cells. Vascul Pharmacol 2018 Mar;102:44-55
Date
01/23/2018Pubmed ID
29355732Pubmed Central ID
PMC6481560DOI
10.1016/j.vph.2018.01.004Scopus ID
2-s2.0-85041619061 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
Endothelium-dependent component of cannabinoid-induced vasodilation has been postulated to require G-protein-coupled non-CB1/CB2 endothelial cannabinoid (eCB) receptor. GPR18 was proposed as a candidate for eCBR. To address the hypothesis that the effects attributed to eCBR are mediated by G-protein-coupled receptor (GPCR)-independent targets, we studied the electrical responses in endothelial cells, focusing on BKCa channels. In patches excised from endothelial-derived EA.hy926 cells, N-arachidonoyl glycine (NAGly) and abnormal cannabidiol (abn-cbd), prototypical agonists for eCB receptor, stimulate single BKCa activity in a concentration- and Ca2+-dependent manner. The postulated eCB receptor inhibitors rimonabant and AM251 were found to inhibit basal and stimulated by NAGly- and abn-cbd BKCa activity in cell-free patches. In isolated mice aortas, abn-cbd and NAGly produced endothelial cell hyperpolarization that was sensitive to paxilline, a selective BKCa inhibitor, but not to GPR18 antibody, and mimicked by NS1619, a direct BKCa opener. In excised patches from mice aortic endothelium, single channel activity with characteristics similar to BKCa was established by the addition of abn-cbd and NAGly. We conclude that the two cannabinoids abn-cbd and NAGly initiate a GPR18-independent activation of BKCa channels in mice aortic endothelial cells that might contribute to vasodilation to cannabinoids.
Author List
Bondarenko AI, Panasiuk O, Drachuk K, Montecucco F, Brandt KJ, Mach FAuthor
Kostiantyn Drachuk Postdoctoral Fellow in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAorta, Thoracic
Arachidonic Acids
Calcium Channel Blockers
Cannabinoid Receptor Agonists
Cannabinoid Receptor Antagonists
Cell Line
Dose-Response Relationship, Drug
Endothelial Cells
Female
Glycine
Human Umbilical Vein Endothelial Cells
Humans
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
Male
Membrane Potentials
Mice, Inbred C57BL
Receptors, Cannabinoid
Resorcinols
Signal Transduction
Vasodilation
