The quest for endothelial atypical cannabinoid receptor: BK Ca channels act as cellular sensors for cannabinoids in in vitro and in situ endothelial cells.

Autor: Bondarenko AI; Circulatory Physiology Department, Bogomoletz Institute of Physiology NAS of Ukraine, Bogomoletz Str 4, Kiev 01024, Ukraine; Institute of Molecular Biology and Biochemistry, Medical University of Graz, Harrachgasse 21/III, Graz, 8010, Austria. Electronic address: abond01@biph.kiev.ua., Panasiuk O; Circulatory Physiology Department, Bogomoletz Institute of Physiology NAS of Ukraine, Bogomoletz Str 4, Kiev 01024, Ukraine., Drachuk K; Circulatory Physiology Department, Bogomoletz Institute of Physiology NAS of Ukraine, Bogomoletz Str 4, Kiev 01024, Ukraine., Montecucco F; First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy; Ospedale Policlinico San Martino, largo Benzi 10, 16132 Genoa, Italy; Centre of Excellence for Biomedical Research (CEBR), University of Genoa, 9 viale Benedetto XV, 16132 Genoa, Italy., Brandt KJ; Division of Cardiology, Foundation for Medical Researches, Department of Internal Medicine, University of Geneva, Av. de la Roseraie 64, CH 1211, Geneva 4, Switzerland., Mach F; Division of Cardiology, Foundation for Medical Researches, Department of Internal Medicine, University of Geneva, Av. de la Roseraie 64, CH 1211, Geneva 4, Switzerland.
Jazyk: angličtina
Zdroj: Vascular pharmacology [Vascul Pharmacol] 2018 Mar; Vol. 102, pp. 44-55. Date of Electronic Publication: 2018 Jan 31.
DOI: 10.1016/j.vph.2018.01.004
Abstrakt: Endothelium-dependent component of cannabinoid-induced vasodilation has been postulated to require G-protein-coupled non-CB 1 /CB 2 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 BK Ca 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 BK Ca activity in a concentration- and Ca 2+ -dependent manner. The postulated eCB receptor inhibitors rimonabant and AM251 were found to inhibit basal and stimulated by NAGly- and abn-cbd BK Ca activity in cell-free patches. In isolated mice aortas, abn-cbd and NAGly produced endothelial cell hyperpolarization that was sensitive to paxilline, a selective BK Ca inhibitor, but not to GPR18 antibody, and mimicked by NS1619, a direct BK Ca opener. In excised patches from mice aortic endothelium, single channel activity with characteristics similar to BK Ca 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 BK Ca channels in mice aortic endothelial cells that might contribute to vasodilation to cannabinoids.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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