Cysteinyl leukotriene receptor 1 is involved in N-methyl-D-aspartate-mediated neuronal injury in mice.
OBJECTIVE
To determine whether cysteinyl leukotriene receptor 1 (CysLT1 receptor) is involved in N-methyl-D-aspartate (NMDA)-induced excitotoxic injury in the mouse brain.


METHODS
Brain injury was induced by NMDA microinjection (50-150 nmol in 0.5 microL) into the cerebral cortex. The changes in CysLT1 receptor expression 24 h after NMDA injection and the effects of a CysLT1 receptor antagonist, pranlukast (0.01 and 0.1 mg/kg), an NMDA receptor antagonist, ketamine (30 mg/kg), and an antioxidant, edaravone (9 mg/kg) were observed.


RESULTS
In the NMDA-injured brain, the CysLT1 receptor mRNA, and protein expression were upregulated, and the receptor was mainly localized in the neurons and not in the astrocytes. Pranlukast, ketamine and edaravone decreased NMDA-induced injury; pranlukast (0.1 mg/kg) and ketamine inhibited the upregulated expression of the CysLT1 receptor.


CONCLUSIONS
CysLT1 receptor expression in neurons is upregulated after NMDA injection, and NMDA-induced responses are inhibited by CysLT1 receptor antagonists, indicating that the increased CysLT1 receptor is involved in NMDA excitotoxicity.
Ding
Qian
Q
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, China. weieq2001@yahoo.com.
Wei
Er-qing
EQ
Zhang
Yan-jun
YJ
Zhang
Wei-ping
WP
Chen
Zhong
Z
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D000983:Antipyrine / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002867:Chromones / Q000494:pharmacology*; D000077553:Edaravone; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D016202:N-Methylaspartate; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018077:Receptors, Leukotriene / Q000096:biosynthesis* / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D015854:Up-Regulation
D000975:Antioxidants; D002867:Chromones; D008565:Membrane Proteins; D012333:RNA, Messenger; D018077:Receptors, Leukotriene; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D007649:Ketamine; C083169:leukotriene D4 receptor; D000077553:Edaravone; D000983:Antipyrine; C047681:pranlukast