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SHR Neuro Cancer Cardio Lipid

Bondarenko, AI; Drachuk, K; Panasiuk, O; Sagach, V; Deak, AT; Malli, R; Graier, WF.
N-Arachidonoyl glycine suppresses Na⁺/Ca²⁺ exchanger-mediated Ca²⁺ entry into endothelial cells and activates BK(Ca) channels independently of GPCRs.
Br J Pharmacol. 2013; 169(4):933-948 [OPEN ACCESS]
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Authors Med Uni Graz:
Bondarenko Oleksandr
Deak Andras Tamas
Graier Wolfgang
Malli Roland
Panasiuk Olga

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Number of Figures: 9
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N-Arachidonoyl glycine (NAGly) is a lipoamino acid with vasorelaxant properties. We aimed to explore the mechanisms of NAGly's action on unstimulated and agonist-stimulated endothelial cells. The effects of NAGly on endothelial electrical signalling were studied in combination with vascular reactivity. In EA.hy926 cells, the sustained hyperpolarization to histamine was inhibited by the non-selective Na⁺/Ca²⁺ exchanger (NCX) inhibitor bepridil and by an inhibitor of reversed mode NCX, KB-R7943. In cells dialysed with Cs⁺-based Na⁺-containing solution, the outwardly rectifying current with typical characteristics of NCX was augmented following histamine exposure, further increased upon external Na⁺ withdrawal and inhibited by bepridil. NAGly (0.3-30 μM) suppressed NCX currents in a URB597- and guanosine 5'-O-(2-thiodiphosphate) (GDPβS)-insensitive manner, [Ca²⁺]i elevation evoked by Na⁺ removal and the hyperpolarization to histamine. In rat aorta, NAGly opposed the endothelial hyperpolarization and relaxation response to ACh. In unstimulated EA.hy926 cells, NAGly potentiated the whole-cell current attributable to large-conductance Ca²⁺-activated K⁺ (BK(Ca)) channels in a GDPβS-insensitive, paxilline-sensitive manner and produced a sustained hyperpolarization. In cell-free inside-out patches, NAGly stimulated single BK(Ca) channel activity. Our data showed that NCX is a Ca²⁺ entry pathway in endothelial cells and that NAGly is a potent G-protein-independent modulator of endothelial electrical signalling and has a dual effect on endothelial electrical responses. In agonist pre-stimulated cells, NAGly opposes hyperpolarization and relaxation via inhibition of NCX-mediated Ca²⁺ entry, while in unstimulated cells, it promotes hyperpolarization via receptor-independent activation of BK(Ca) channels. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Aorta - drug effects
Arachidonic Acids - pharmacology
Calcium Channel Blockers - pharmacology
Calcium Signaling - drug effects
Cell Line -
Cell Membrane - drug effects
Cell-Free System - drug effects
Endothelium, Vascular - drug effects
Glycine - analogs & derivatives
Histamine - metabolism
Human Umbilical Vein Endothelial Cells -
Humans -
In Vitro Techniques -
Large-Conductance Calcium-Activated Potassium Channels - agonists
Male -
Membrane Potentials - drug effects
Muscle, Smooth, Vascular - drug effects
Rats -
Rats, Wistar -
Receptors, G-Protein-Coupled - metabolism
Sodium-Calcium Exchanger - antagonists & inhibitors
Vasoconstriction - drug effects
Vasodilator Agents - pharmacology

Find related publications in this database (Keywords)
N-arachidonoyl glycine
membrane potential
BKCa channels
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