Abstract
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.
Similar content being viewed by others
Article PDF
References
Carlson NG, Wieggel WA, Chen J, Bacchi A, Rogers SW, Gahring LC . Inflammatory cytokines IL–1 alpha, IL–1 beta, IL–6, and TNF-alpha impart neuroprotection to an excitotoxin through distinct pathways. J Immunol 1999; 163: 3963–8.
Gucuyener K, Atalay Y, Aral YZ, Hasanoglu A, Turkyilmaz C, Biberoglu G . Excitatory amino acids and taurine levels in cerebrospinal fluid of hypoxic ischemic encephalopathy in newborn. Clin Neurol Neurosurg 1999; 101: 171–4.
Favalli L, Rozza A, Frattini P, Masoero E, Scelsi R, Pascale A, et al. Ischemia-induced glutamate release in rat frontoparietal cortex after chronic alcohol and withdrawal. Neurosci Lett 2002; 326: 183–6.
Galasso JM, Liu Y, Szaflarski J, Warren JS, Silverstein FS . Monocyte chemoattractant protein–1 is a mediator of acute excitotoxic injury in neonatal rat brain. Neuroscience 2000; 101: 737–44.
Jander S, Schroeter M, Stoll G . Role of NMDA receptor signaling in the regulation of inflammatory gene expression after focal brain ischemia. J Neuroimmunol 2000; 109: 181–7.
Acarin L, Gonzalez B, Castellano B . Decrease of proinflammatory molecules correlates with neuroprotective effect of the fluorinated salicylate triflusal after postnatal excitotoxic damage. Stroke 2002; 33: 2499–505.
Mabe H, Nagai H, Suzuka T . Role of brain tissue leukotriene in brain oedema following cerebral ischaemia: effect of a 5-lipoxygenase inhibitor, AA-861. Neurol Res 1990; 12: 165–8.
Baba T, Black KL, Ikezaki K, Chen KN, Becker DP . Intracarotid infusion of leukotriene C4 selectively increases blood-brain barrier permeability after focal ischemia in rats. J Cereb Blood Flow Metab 1991; 11: 638–43.
Rao AM, Hatcher JF, Kindy MS, Dempsey RJ . Arachidonic acid and leukotriene C4: role in transient cerebral ischemia of gerbils. Neurochem Res 1999; 24: 1225–32.
Ciceri P, Rabuffetti M, Monopoli A, Nicosia S . Production of leukotrienes in a model of focal cerebral ischaemia in the rat. Br J Pharmacol 2001; 133: 1323–9.
Di Gennaro A, Carnini C, Buccellati C, Ballerio R, Zarini S, Fumagalli F, et al. Cysteinyl-leukotrienes receptor activation in brain inflammatory reactions and cerebral edema formation: a role for transcellular biosynthesis of cysteinyl-leukotrienes. FASEB J 2004; 18: 842–4.
Ge QF, Wei EQ, Zhang WP, Hu X, Huang XJ, Zhang L, et al. Activation of 5-lipoxygenase after oxygen-glucose deprivation is partly mediated via NMDA receptor in rat cortical neurons. J Neurochem 2006; 97: 992–1004.
Brink C, Dahlen SE, Drazen J, Evans JF, Hay DW, Nicosia S, et al. International Union of Pharmacology XXXVII. Nomenclature for leukotriene and lipoxin receptors. Pharmacol Rev 2003; 55: 195–227.
Lynch KR, O'Neill GP, Liu Q, Im DS, Sawyer N, Metters KM, et al. Characterization of the human cysteinyl leukotriene CysLT1 receptor. Nature 1999; 399: 789–93.
Sarau HM, Ames RS, Chambers J, Ellis C, Elshourbagy N, Foley JJ, et al. Identification, molecular cloning, expression, and characterization of a cysteinyl leukotriene receptor. Mol Pharmacol 1999; 56: 657–63.
Zhang WP, Hu H, Zhang L, Ding W, Yao HT, Chen KD, et al. Expression of cysteinyl leukotriene receptor 1 in human traumatic brain injury and brain tumors. Neurosci Lett 2004; 363: 247–51.
Zeng LH, Zhang WP, Wang RD, Wang PL, Wei EQ . Protective effect of ONO-1078, a leukotriene antagonist, on focal cerebral ischemia in mice. Yao Xue Xue Bao 2001; 36: 148–50. Chinese.
Zhang WP, Wei EQ, Mei RH, Zhu CY, Zhao MH . Neuroprotective effect of ONO–1078, a leukotriene receptor antagonist, on focal cerebral ischemia in rats. Acta Pharmacol Sin 2002; 23: 871–7.
Zhang LH, Wei EQ . Neuroprotective effect of ONO-1078, a leukotriene receptor antagonist, on transient global cerebral ischemia in rats. Acta Pharmacol Sin 2003; 24: 1241–7.
Yu GL, Wei EQ, Zhang SH, Xu HM, Chu LS, Zhang WP, et al. Montelukast, a cysteinyl leukotriene receptor-1 antagonist, dose-and time-dependently protects against focal cerebral ischemia in mice. Pharmacology 2005; 73: 31–40.
Zhang LH, Wei EQ . ONO-1078 reduces NMDA-induced brain injury and vascular cell adhesion molecule-1 expression in rats. Acta Pharmacol Sin 2005; 26: 435–40.
Toyoda K, Fujii K, Kamouchi M, Nakane H, Arihiro S, Okada Y, et al. Free radical scavenger, edaravone, in stroke with internal carotid artery occlusion. J Neurol Sci 2004; 221: 11–7.
Yasuoka N, Nakajima W, Ishida A, Takada G . Neuroprotection of edaravone on hypoxic-ischemic brain injury in neonatal rats. Dev Brain Res 2004; 151: 129–39.
Iadecola C, Niwa K, Nogawa S, Zhao X, Nagayama M, Araki E, et al. Reduced susceptibility to ischemic brain injury and N-methyl-D-aspartate-mediated neurotoxicity in cyclooxygenase-2-deficient mice. Proc Natl Acad Sci USA 2001; 98: 1294–9.
Lin TN, He YY, Wu G, Khan M, Hsu CY . Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats. Stroke 1993; 24: 117–21.
Ogasawara H, Ishii S, Yokomizo T, Kakinuma T, Komine M, Tamaki K, et al. Characterization of mouse cysteinyl leukotriene receptors mCysLT1 and mCysLT2: differential pharmacological properties and tissue distribution. J Biol Chem 2002; 277: 18763–8.
Mazzetti L, Franchi-Micheli S, Nistri S, Quattrone S, Simone R, Ciuffi M, et al. The ACh-induced contraction in rat aortas is mediated by the Cys Lt1 receptor via intracellular calcium mobilization in smooth muscle cells. Br J Pharmacol 2003; 138: 707–15.
Ohd JF, Nielsen CK, Campbell J, Landberg G, Lofberg H, Sjolander A . Expression of the leukotriene D4 receptor CysLT1, COX-2, and other cell survival factors in colorectal adenocarcinomas. Gastroenterology 2003; 124: 57–70.
Zhang YJ, Zhang L, Wang SB, Shen HH, Wei EQ . Montelukast modulates lung CysLT1 receptor expression and eosinophilic inflammation in asthmatic mice. Acta Pharmacol Sin 2004; 25: 1341–6.
Thivierge M, Doty M, Johnson J, Stankova J, Rola-Pleszczynski M . IL-5 up-regulates cysteinyl leukotriene 1 receptor expression in HL-60 cells differentiated into eosinophils. J Immunol 2000; 165: 5221–6.
Fukushima C, Matsuse H, Hishikawa Y, Kondo Y, Machida I, Saeki S, et al. Pranlukast, a leukotriene receptor antagonist, inhibits interleukin-5 production via a mechanism distinct from leukotriene receptor antagonism. Int Arch Allergy Immunol 2005; 136: 165–72.
Church J, Zeman S, Lodge D . The neuroprotective action of ketamine and MK-801 after transient cerebral ischemia in rats. Anesthesiology 1988; 69: 702–9.
Proescholdt M, Heimann A, Kempski O . Neuroprotection of S (+) ketamine isomer in global forebrain ischemia. Brain Res 2001; 904: 245–51.
Shapira Y, Lam AM, Eng CC, Laohaprasit V, Michel M . Therapeutic time window and dose response of the beneficial effects of ketamine in experimental head injury. Stroke 1994; 25: 1637–43.
Leander JD, Lawson RR, Ornstein PL, Zimmerman DM . N-methyl-D-aspartic acid-induced lethality in mice: selective antagonism by phencyclidine-like drugs. Brain Res 1988; 448: 115–20.
Lees GJ . Influence of ketamine on the neuronal death caused by NMDA in the rat hippocampus. Neuropharmacology 1995; 34: 411–7.
Lees GJ . Effects of ketamine on the in vivo toxicity of quinolinate and N-methyl-D-aspartate in the rat hippocampus. Neurosci Lett 1987; 78: 180–6.
Wu TW, Zeng LH, Wu J, Fung KP . MCI-186: further histochemical and biochemical evidence of neuroprotection. Life Sci 2000; 67: 2387–92.
Ikeda T, Xia YX, Kaneko M, Sameshima H, Ikenoue T . Effect of the free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), on hypoxia-ischemia-induced brain injury in neonatal rats. Neurosci Lett 2002; 329: 33–6.
Author information
Authors and Affiliations
Corresponding author
Additional information
Project supported by the National Natural Science Foundation of China (No 30371637).
Rights and permissions
About this article
Cite this article
Ding, Q., Wei, Eq., Zhang, Yj. et al. Cysteinyl leukotriene receptor 1 is involved in N-methyl-D-aspartate-mediated neuronal injury in mice. Acta Pharmacol Sin 27, 1526–1536 (2006). https://doi.org/10.1111/j.1745-7254.2006.00438.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2006.00438.x
Keywords
This article is cited by
-
Exploring the neuroprotective effects of montelukast on brain inflammation and metabolism in a rat model of quinolinic acid-induced striatal neurotoxicity
Journal of Neuroinflammation (2023)
-
The Novel Potential Therapeutic Utility of Montelukast in Alleviating Autistic Behavior Induced by Early Postnatal Administration of Thimerosal in Mice
Cellular and Molecular Neurobiology (2021)
-
Cysteinyl leukotriene correlated with 8-isoprostane levels as predictive biomarkers for sensory dysfunction in autism
Lipids in Health and Disease (2016)
-
Montelukast, a Cysteinyl Leukotriene Receptor-1 Antagonist Protects Against Hippocampal Injury Induced by Transient Global Cerebral Ischemia and Reperfusion in Rats
Neurochemical Research (2015)