Direct activation of Ca <superscript>2+</superscript> and voltage-gated potassium channels of large conductance by anandamide in endothelial cells does not support the presence of endothelial atypical cannabinoid receptor.
In: European journal of pharmacology, Jg. 805 (2017-06-15), S. 14-24
Online
academicJournal
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 BK Ca 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 BK Ca 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 BK Ca opener. The action does not require cell integrity or integrins and is caused by direct modification of BK Ca channel activity.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Titel: |
Direct activation of Ca <superscript>2+</superscript> and voltage-gated potassium channels of large conductance by anandamide in endothelial cells does not support the presence of endothelial atypical cannabinoid receptor.
|
---|---|
Autor/in / Beteiligte Person: | Bondarenko, AI ; Panasiuk, O ; Okhai, I ; Montecucco, F ; Brandt, KJ ; Mach, F |
Link: | |
Zeitschrift: | European journal of pharmacology, Jg. 805 (2017-06-15), S. 14-24 |
Veröffentlichung: | 2005- : Amsterdam : Elsevier Science ; <i>Original Publication</i>: Amsterdam, North Holland Pub. Co., 2017 |
Medientyp: | academicJournal |
ISSN: | 1879-0712 (electronic) |
DOI: | 10.1016/j.ejphar.2017.03.038 |
Schlagwort: |
|
Sonstiges: |
|