Activation of Dopamine D4 Receptors Is Protective Against Hypoxia/Reoxygenation-Induced Cell Death in HT22 Cells

Journal of Pharmacological Sciences

Kumiko Ishige¹  Yoshihisa Ito¹  Mioko Hirabayashi¹  Saori Shimada¹  Yasuhiro Kosuge¹  Tetsuro Kihara¹ 

[1] Research Unit of Pharmacology, Department of Clinical Pharmacy, School of Pharmacy, Nihon University, Japan

关键词: dopamine D4 receptor;    hypoxia/reoxygenation;    apomorphine;    oxidative stress;    cell death;   

DOI  :  10.1254/jphs.10134FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(32)Cited-By(7)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 D4-receptor antagonist but not by D2- or D3-receptor antagonists. In addition, PD168077, a selective dopamine D4–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 D4 receptors protects against H/R-induced cell death in HT22 cells.

【 授权许可】

Unknown