Acta Pharmacologica Sinica 2006 December; 27 (12): 1526-1536; doi: 10.1111/j.1745-7254.2006.00438.x

Aim: 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 µL) 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.

Conclusion: 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.

Keywords: cysteinyl leukotriene receptor; excitotoxi-city; N-methyl-D-aspartate; leukotriene receptor antagonist; pranlukast; NMDA receptor antagonist; ketamine