Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Bondarenko, AI; Panasiuk, O; Okhai, I; Montecucco, F; Brandt, KJ; Mach, F.
Direct activation of Ca(2+) and voltage-gated potassium channels of large conductance by anandamide in endothelial cells does not support the presence of endothelial atypical cannabinoid receptor.
Eur J Pharmacol. 2017; 805(4):14-24
Web of Science PubMed FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Bondarenko Oleksandr
Panasiuk Olga
Gendermonitor:
Altmetrics:

Dimensions Citations:
Abstract:
Endocannabinoid anandamide induces endothelium-dependent relaxation commonly attributed to stimulation of the G-protein coupled endothelial anandamide receptor. The study addressed the receptor-independent effect of anandamide on large conductance Ca(2+)-dependent K(+) channels expressed in endothelial cell line EA.hy926. Under resting conditions, 10µM anandamide did not significantly influence the resting membrane potential. In a Ca(2+)-free solution the cells were depolarized by ~10mV. Further administration of 10µM anandamide hyperpolarized the cells by ~8mV. In voltage-clamp mode, anandamide elicited the outwardly rectifying whole-cell current sensitive to paxilline but insensitive to GDPβS, a G-protein inhibitor. Administration of 70µM Mn(2+), an agent used to promote integrin clustering, reversibly stimulated whole-cell current, but failed to further facilitate the anandamide-stimulated current. In an inside-out configuration, anandamide (0.1-30µM) facilitated single BKCa channel activity in a concentration-dependent manner within a physiological Ca(2+) range and a wide range of voltages, mainly by reducing mean closed time. The effect is essentially eliminated following chelation of Ca(2+) from the cytosolic face and pre-exposure to cholesterol-reducing agent methyl-β-cyclodextrin. O-1918 (3µM), a cannabidiol analog used as a selective antagonist of endothelial anandamide receptor, reduced BKCa channel activity in inside-out patches. These results do not support the existence of endothelial cannabinoid receptor and indicate that anandamide acts as a direct BKCa opener. The action does not require cell integrity or integrins and is caused by direct modification of BKCa channel activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Find related publications in this database (Keywords)
Anandamide
Endothelial cannabinoid receptor
Integrins
BKCa channels
© Meduni Graz Impressum