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Acta Physiologica 2012; Volume 204, Supplement 689
91st Annual Meeting of The German Physiological Society
3/22/2012-3/25/2012
Dresden, Germany
ENHANCED CATECHOLAMINE RELEASE IN MICE EXPRESSING PKB/SGK-RESISTANT GSK3
Abstract number: P058
Ahmed1 *M., Siraskar1 B., Volkl1 J., Hierlmeier1 M., Gu1 S., Schmid1 E., Leibrock1 C., Foller1 M., Lang1 U., Lang1 F.
1University of Tbingen, Department of Physiology, Tbingen, Germany
Glycogen synthase kinase 3 (GSK3) plays a decisive role in the regulation of multiple functions. GSK3 is phosphorylated and its activity inhibited by protein kinase B (PKB/Akt) and serum and glucocorticoid inducible kinase (SGK) isoforms, which are in turn activated by growth factors through phosphoinositide (PI) 3 kinase signaling. PI3/PKB/Akt/SGK-dependent inhibition of GSK3 is disrupted in gene-targeted knockin mice with mutated and thus PKB/SGK-resistant GSK3a,ß (gsk3KI) where the serine of the PKB/SGK phosphorylation site has been replaced by alanine. Recent experiments revealed that blood pressure is significantly higher in those mice than in wild type mice (gsk3WT). The present study was performed to elucidate the underlying cause. Blood pressure was determined with the tail cuff method, heart rate by ECG measurements, catecholamine concentrations by ELISA, and vanillylmandelic acid by high pressure liquid chromatography. As a result, blood pressure and heart rate were significantly higher in gsk3KI than in gsk3WT mice. The a-adrenergic blocker prazosin (1 mg/g body weight, b.w.) and the ganglion blocker hexamethonium (40 mg/g b.w.) decreased blood pressure to a larger extent in gsk3KI than in gsk3WT mice and virtually abrogated the difference between genotypes. Similarly, the b-adrenergic blocker atenolol (5 mg/g b.w.) decreased the heart rate to a larger extent in gsk3KI than in gsk3WT mice and again dissipated the difference of heart rate between genotypes. Plasma epinephrine and norepinephrine concentrations, as well as urinary excretion of vanillylmandelic acid, were significantly higher in gsk3KI than in gsk3WT mice. The observations reveal a completely novel function of PKB/Akt/SGK-dependent GSK3 signaling, i.e., regulation of catecholamine release.
To cite this abstract, please use the following information:
Acta Physiologica 2012; Volume 204, Supplement 689 :P058