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SHR Neuro Krebs Kardio Lipid

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(+)-Ca(2+) exchanger and endoplasmic reticulum Ca(2+) refilling.
VASC PHARMACOL. 2017; 89(1): 39-48.
Web of Science PubMed FullText FullText_MUG


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

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Plum Analytics:
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(+)/Ca(2+) 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 Ca(2+)-dependent K(+) channels of intermediate and small conductance. The hyperpolarizing responses to consecutive histamine applications are strongly reduced by NCX inhibition. In a Ca(2+)-re-addition protocol, bepridil, a NCX inhibitor, and KB-R7943, a blocker of reversed NCX, inhibit the hyperpolarizing responses to Ca(2+)-re-addition following Ca(2+) 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 Ca(2+) 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 (Keywords)
Endothelial cells
Na+-Ca2+ exchanger
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