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SHR Neuro Cancer Cardio Lipid Metab Microb
Bondarenko, A; Waldeck-Weiermair, M; Naghdi, S; Poteser, M; Malli, R; Graier, WF.
GPR55-dependent and -independent ion signalling in response to lysophosphatidylinositol in endothelial cells.
Br J Pharmacol. 2010; 161(2): 308-320.
Doi: 10.1111/j.1476-5381.2010.00744.x
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- Leading authors Med Uni Graz
- Bondarenko Oleksandr
- Graier Wolfgang
- Co-authors Med Uni Graz
- Malli Roland
- Naghdi Shamim
- Poteser Michael
- Waldeck-Weiermair Markus
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- Abstract:
- Background and purpose: The glycerol-based lysophospholipid lysophosphatidylinositol (LPI) is an endogenous agonist of the G-protein-coupled receptor 55 (GPR55) exhibiting cannabinoid receptor-like properties in endothelial cells. To estimate the contribution of GPR55 to the physiological effects of LPI, the GPR55-dependent and -independent electrical responses in this cell type were investigated. Experimental approach: Applying small interference RNA-mediated knock-down and transient overexpression, GPR55-dependent and -independent effects of LPI on cytosolic free Ca2+ concentration, membrane potential and transmembrane ion currents were studied in EA.hy296 cells. Key results: In a GPR55-dependent, GDP beta S and U73122-sensitive manner, LPI induced rapid and transient intracellular Ca2+ release that was associated with activation of charybdotoxin-sensitive, large conductance, Ca2+-activated, K+ channels (BK(Ca)) and temporary membrane hyperpolarization. Following these initial electrical reactions, LPI elicited GPR55-independent long-lasting Na+ loading and a non-selective inward current causing sustained membrane depolarization that depended on extracellular Ca2+ and Na+ and was partially inhibited by Ni2+ and La3+. This inward current was due to the activation of a voltage-independent non-selective cation current. The Ni2+ and La3+-insensitive depolarization with LPI was prevented by inhibition of the Na/K-ATPase by ouabain. Conclusions and implications: LPI elicited a biphasic response in endothelial cells of which the immediate Ca2+ signalling depends on GPR55 while the subsequent depolarization is due to Na+ loading via non-selective cation channels and an inhibition of the Na/K-ATPase. Thus, LPI is a potent signalling molecule that affects endothelial functions by modulating several cellular electrical responses that are only partially linked to GPR55.
- Find related publications in this database (using NLM MeSH Indexing)
- Calcium - metabolism
- Calcium Signaling - drug effects Calcium Signaling - physiology
- Cell Line -
- Cytosol - drug effects Cytosol - metabolism Cytosol - physiology
- Endothelial Cells - drug effects Endothelial Cells - metabolism Endothelial Cells - physiology
- Humans -
- Ion Transport - drug effects Ion Transport - physiology
- Lysophospholipids - pharmacology Lysophospholipids - physiology
- Membrane Potentials - drug effects Membrane Potentials - physiology
- Potassium Channels, Calcium-Activated - metabolism
- RNA, Small Interfering -
- Receptors, G-Protein-Coupled - agonists Receptors, G-Protein-Coupled - antagonists and inhibitors Receptors, G-Protein-Coupled - genetics Receptors, G-Protein-Coupled - physiology
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- Find related publications in this database (Keywords)
- endothelial cells
- GPR55
- lysophospholipid signalling
- membrane potential
- non-selective cation channel
- patch-clamp
- rimonabant