Activation of dopamine D4 receptors is protective against hypoxia/reoxygenation-induced cell death in HT22 cells.
J Pharmacol Sci
; 114(2): 217-24, 2010.
Article
em En
| MEDLINE
| ID: mdl-20921819
ABSTRACT
Several reports have shown that some dopamine receptor ligands modulate the ischemia-reperfusion injury in animal models; however, its underling mechanisms are still unclear. In this study, we sought to establish an in vitro experimental model of hypoxia/reoxygenation (H/R) using HT22 cells that originated from mouse hippocampal neurons and to examine protective the effect of dopamine-receptor ligands against H/R-induced cell injury. The treatment with hypoxia for 18 h followed by reoxygenation for 6 h induced the elevation of intracellular reactive oxygen species (ROS) and reduction of mitochondrial membrane potential; however, lactate dehydrogenase (LDH) release was not changed at this time point. LDH release was increased after reoxygenation for 18 h and longer, and this increase in LDH release was suppressed by dopamine receptor agonists such as apomorphine and apocodeine. The suppressive effects of these agonists were reversibly inhibited by L750667, a D(4)-receptor antagonist but not by D(2)- or D(3)-receptor antagonists. In addition, PD168077, a selective dopamine D(4)-receptor agonist, also protected against H/R-induced cell death. These results suggest that H/R causes oxidative stress-induced cell death and that the activation of dopamine D(4) receptors protects against H/R-induced cell death in HT22 cells.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão
/
Receptores de Dopamina D4
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Pharmacol Sci
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Japão