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SHR Neuro Cancer Cardio Lipid Metab Microb

Bondarenko, AI; Montecucco, F; Panasiuk, O; Sagach, V; Sidoryak, N; Brandt, KJ; Mach, F.
GPR55 agonist lysophosphatidylinositol and lysophosphatidylcholine inhibit endothelial cell hyperpolarization via GPR-independent suppression of Na⁺-Ca²⁺ exchanger and endoplasmic reticulum Ca²⁺ refilling.
Vascul Pharmacol. 2017; 89(2):39-48 Doi: 10.1016/j.vph.2017.01.002 [OPEN ACCESS]
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Leading authors Med Uni Graz: Bondarenko Oleksandr
Co-authors Med Uni Graz: Panasiuk Olga
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Abstract:: Lysophosphatidylinositol (LPI) and lysophosphatidylcholine (LPC) are lipid signaling molecules that induce endothelium-dependent vasodilation. In addition, LPC suppresses acetylcholine (Ach)-induced responses. We aimed to determine the influence of LPC and LPI on hyperpolarizing responses in vitro and in situ endothelial cells (EC) and identify the underlying mechanisms. Using patch-clamp method, we show that LPI and LPC inhibit EC hyperpolarization to histamine and suppress Na⁺/Ca²⁺ exchanged (NCX) currents in a concentration-dependent manner. The inhibition is non-mode-specific and unaffected by intracellular GDPβS infusion and tempol, a superoxide dismutase mimetic. In excised mouse aorta, LPI strongly inhibits the sustained and the peak endothelial hyperpolarization induced by Ach, but not by SKA-31, an opener of Ca²⁺-dependent K⁺ channels of intermediate and small conductance. The hyperpolarizing responses to consecutive histamine applications are strongly reduced by NCX inhibition. In a Ca²⁺-re-addition protocol, bepridil, a NCX inhibitor, and KB-R7943, a blocker of reversed NCX, inhibit the hyperpolarizing responses to Ca²⁺-re-addition following Ca²⁺ stores depletion. These finding indicate that LPC and LPI inhibit endothelial hyperpolarization to Ach and histamine independently of G-protein coupled receptors and superoxide anions. Reversed NCX is critical for ER Ca²⁺ refilling in EC. The inhibition of NCX by LPI and LPC underlies diminished endothelium-dependent responses and endothelial dysfunction accompanied by increased levels of these lipids in the blood. Copyright © 2017 Elsevier Inc. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing): Acetylcholine - pharmacology; Animals -; Aorta, Thoracic - drug effects; Aorta, Thoracic - metabolism; Calcium Signaling - drug effects; Dose-Response Relationship, Drug -; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - metabolism; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Female -; Histamine - pharmacology; In Vitro Techniques -; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits - agonists; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits - metabolism; Lysophosphatidylcholines - pharmacology; Lysophospholipids - pharmacology; Male -; Membrane Potentials -; Mice, Inbred C57BL -; Receptors, Cannabinoid - drug effects; Receptors, Cannabinoid - metabolism; Sodium-Calcium Exchanger - antagonists & inhibitors; Sodium-Calcium Exchanger - metabolism; Vasodilation - drug effects; Vasodilator Agents - pharmacology
Find related publications in this database (Keywords): Lysophosphatidylinositol; Lysophosphatidylcholine; Endothelial cells; Hyperpolarization; Na+-Ca2+ exchanger