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Waldeck-Weiermair, M; Zoratti, C; Osibow, K; Balenga, N; Goessnitzer, E; Waldhoer, M; Malli, R; Graier, WF.
Integrin clustering enables anandamide-induced Ca2+ signaling in endothelial cells via GPR55 by protection against CB1-receptor-triggered repression.
J Cell Sci. 2008; 121(Pt 10): 1704-1717. [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Aghaei Bandbon Balenga Nariman
Graier Wolfgang
Malli Roland
Osibow Karin
Waldeck-Weiermair Markus
Waldhoer Maria

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Number of Figures: 10
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Although the endocannabinoid anandamide is frequently described to act predominantly in the cardiovascular system, the molecular mechanisms of its signaling remained unclear. In human endothelial cells, two receptors for anandamide were found, which were characterized as cannabinoid 1 receptor (CB1R; CNR1) and G-protein-coupled receptor 55 (GPR55). Both receptors trigger distinct signaling pathways. It crucially depends on the activation status of integrins which signaling cascade becomes promoted upon anandamide stimulation. Under conditions of inactive integrins, anandamide initiates CB1R-derived signaling, including Gi-protein-mediated activation of spleen tyrosine kinase (Syk), resulting in NFkappaB translocation. Furthermore, Syk inhibits phosphoinositide 3-kinase (PI3K) that represents a key protein in the transduction of GPR55-originated signaling. However, once integrins are clustered, CB1R splits from integrins and, thus, Syk cannot further inhibit GPR55-triggered signaling resulting in intracellular Ca2+ mobilization from the endoplasmic reticulum (ER) via a PI3K-Bmx-phospholipase C (PLC) pathway and activation of nuclear factor of activated T-cells. Altogether, these data demonstrate that the physiological effects of anandamide on endothelial cells depend on the status of integrin clustering.
Find related publications in this database (using NLM MeSH Indexing)
1-Phosphatidylinositol 3-Kinase - metabolism
Arachidonic Acids - metabolism
Calcium Signaling - drug effects
Cell Line -
Endocannabinoids - pharmacology
Endothelial Cells - cytology
Humans -
Integrins - metabolism
Intracellular Signaling Peptides and Proteins - metabolism
Polyunsaturated Alkamides - metabolism
Protein-Serine-Threonine Kinases - drug effects
Protein-Tyrosine Kinases - metabolism
Receptor, Cannabinoid, CB1 - metabolism
Receptors, G-Protein-Coupled - metabolism
Signal Transduction - drug effects

Find related publications in this database (Keywords)
cannabinoid signaling
CB1 receptor
Ca2+ signaling
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