Creatine increases hippocampal Na(+),K(+)-ATPase activity via NMDA-calcineurin pathway.

Autor: Rambo LM; Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil., Ribeiro LR, Schramm VG, Berch AM, Stamm DN, Della-Pace ID, Silva LF, Furian AF, Oliveira MS, Fighera MR, Royes LF
Jazyk: angličtina
Zdroj: Brain research bulletin [Brain Res Bull] 2012 Sep 01; Vol. 88 (6), pp. 553-9. Date of Electronic Publication: 2012 Jun 26.
DOI: 10.1016/j.brainresbull.2012.06.007
Abstrakt: Achievements made over the past few years have demonstrated the important role of the creatine and phosphocreatine system in the buffering and transport of high-energy phosphates into the brain; however, the non-energetic processes elicited by this guanidine compound in the hippocampus are still poorly understood. In the present study we disclosed that the incubation of rat hippocampal slices with creatine (10mM) for 30 min increased Na(+),K(+)-ATPase activity. In addition, intrahippocampal injection of creatine (5 nmol/site) also increased the above-mentioned activity. The incubation of hippocampal slices with N-methyl-d-aspartate (NMDA; MK-801, 10 μM) and NMDA Receptor 2B (NR2B; ifenprodil, 3 μM) antagonists but not with the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA)/kainate antagonist (DNQX, 10 μM) and nitric oxide synthase inhibitor (NOS; l-NAME, 100 μM), blunted the effect of creatine on Na(+),K(+)-ATPase activity. Furthermore, the calcineurin inhibitor (cyclosporine A, 200 nM) as well as the Protein Kinase C (PMA, 100 nM) and Protein Kinase A (8-Br-cAMP, 30 μM) activators attenuated the creatine-induced increase of Na(+),K(+)-ATPase activity. In addition, the incubation of hippocampal slices with creatine (10mM) for 30 min increased calcineurin activity. The results presented here suggest that creatine increases Na(+),K(+)-ATPase activity via NMDA-calcineurin pathway, proposing an putative underlying non-energetic role of this guanidine compound. However, more studies are needed to assess the contribution of this putative alternative role in neurological diseases that present decreased Na(+),K(+)-ATPase activity.
(Copyright © 2012 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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