Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Wascher, TC; Toplak, H; Krejs, GJ; Simecek, S; Kukovetz, WR; Graier, WF.
Intracellular mechanisms involved in D-glucose-mediated amplification of agonist-induced Ca2+ response and EDRF formation in vascular endothelial cells.
Diabetes. 1994; 43(8):984-991
Doi: 10.2337/diabetes.43.8.984
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- Führende Autor*innen der Med Uni Graz
- Wascher Thomas
- Co-Autor*innen der Med Uni Graz
- Graier Wolfgang
- Krejs Günter Josef
- Toplak Hermann
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- Abstract:
- Prolonged treatment of vascular endothelial cells with pathologically high D-glucose amplifies autacoid-induced Ca2+ mobilization and thus formation of nitric oxide. This study investigated the Ca2+ source for the change in endothelial CA2+ response on agonist stimulation. Pretreatment with high D-glucose (44 vs. 5 mM) enhanced release of intracellular Ca2+ by bradykinin as a result of a 2.0-fold increased formation of inositol 1,4,5-trisphosphate. High D-glucose also amplified Ca2+ influx (2.0-fold). In high D-glucose preincubated cells, stimulation with bradykinin significantly increased transplasmalemmal 45Ca2+ flux (3.2-fold) and caused a 2.0-fold increase in permeability to Mn2+, a surrogate for endothelial plasma membrane Ca2+ channels. A significant 2.0-fold increase occurred in the maximal slope, suggesting a higher rate of Mn2+ (Ca2+) influx. Ca2+ influx, stimulated by an inositol phosphate-independent depletion of intracellular Ca2+ stores with 2,5-di-(tert-butyl)-hydroquinone was also significantly increased 2.4-fold by high D-glucose, with no effect on intracellular Ca2+ release. D-glucose failed to modulate resting or stimulated cAMP levels. We suggest that prolonged exposure to pathologically high D-glucose increases formation of inositol polyphosphates, thus increasing Ca2+ release. Ca2+ entry is increased by amplification of unknown signal transduction mechanisms triggered by Ca2+ store depletion.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
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- Bradykinin - pharmacology
- Calcium - metabolism
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- Cell Membrane - metabolism
- Cell Membrane Permeability - drug effects
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- Cyclic AMP - biosynthesis
- Egtazic Acid - pharmacology
- Endothelium, Vascular - drug effects Endothelium, Vascular - metabolism
- Glucose - pharmacology
- Inositol 1,4,5-Trisphosphate - biosynthesis
- Manganese - metabolism
- Nitric Oxide - biosynthesis
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