کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5554694 | 1558875 | 2017 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Direct activation of Ca2+ and voltage-gated potassium channels of large conductance by anandamide in endothelial cells does not support the presence of endothelial atypical cannabinoid receptor
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موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Direct activation of Ca2+ and voltage-gated potassium channels of large conductance by anandamide in endothelial cells does not support the presence of endothelial atypical cannabinoid receptor Direct activation of Ca2+ and voltage-gated potassium channels of large conductance by anandamide in endothelial cells does not support the presence of endothelial atypical cannabinoid receptor](/preview/png/5554694.png)
چکیده انگلیسی
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 Ca2+-dependent K+ channels expressed in endothelial cell line EA.hy926. Under resting conditions, 10 µM anandamide did not significantly influence the resting membrane potential. In a Ca2+-free solution the cells were depolarized by ~10 mV. Further administration of 10 µM anandamide hyperpolarized the cells by ~8 mV. 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 70 µM Mn2+, 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 (0.1-30 µM) facilitated single BKCa channel activity in a concentration-dependent manner within a physiological Ca2+ range and a wide range of voltages, mainly by reducing mean closed time. The effect is essentially eliminated following chelation of Ca2+ from the cytosolic face and pre-exposure to cholesterol-reducing agent methyl-β-cyclodextrin. O-1918 (3 µM), 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 805, 15 June 2017, Pages 14-24
Journal: European Journal of Pharmacology - Volume 805, 15 June 2017, Pages 14-24
نویسندگان
Alexander I. Bondarenko, Olga Panasiuk, Iryna Okhai, Fabrizio Montecucco, Karim J. Brandt, Francois Mach,