Cysteinyl leukotriene receptor 1 is involved in n-methyl-d-aspartate-mediated neuronal injury in mice

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 EDONERPIC MALEATE REGULATES GLUTAMATE RECEPTORS THROUGH CRMP2- AND ARC-MEDIATED MECHANISMS IN RESPONSE TO BRAIN TRAUMA Article Open

access 04 March 2022 GLUTAMATE ACTS ON ACID-SENSING ION CHANNELS TO WORSEN ISCHAEMIC BRAIN INJURY Article Open access 10 July 2024 THE PHOSPHODIESTERASE-4 AND GLYCINE TRANSPORTER-1

INHIBITORS ENHANCE IN VIVO HIPPOCAMPAL THETA NETWORK CONNECTIVITY AND SYNAPTIC PLASTICITY, WHEREAS D-SERINE DOES NOT Article Open access 18 June 2020 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. CAS  PubMed  Google Scholar  * 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. Article  CAS  Google Scholar  * 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. Article  CAS  Google Scholar 

* 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. Article  CAS  Google Scholar  * 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. Article  CAS  Google Scholar  * 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. Article  CAS  Google Scholar  * 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. Article  CAS  Google Scholar  * 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.

Article  CAS  Google Scholar  * 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. Article  CAS  Google Scholar  * 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. Article  CAS  Google Scholar  * 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. Article  CAS  Google Scholar  * 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. Article  CAS  Google Scholar  * 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. Article  CAS  Google Scholar  * 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. Article  CAS  Google Scholar  * 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. Article  CAS  Google Scholar  * 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. Article  CAS 

Google Scholar  * 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. CAS  PubMed  Google Scholar  * 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. CAS  PubMed  Google Scholar  * 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. CAS  PubMed  Google Scholar  * 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. Article  CAS  Google Scholar  * 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. Article  Google Scholar  * 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. Article  CAS  Google

Scholar  * 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. Article  CAS  Google

Scholar  * 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. Article  CAS  Google Scholar  * 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. Article  CAS  Google Scholar  * 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. Article  CAS  Google Scholar

  * 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. Article  CAS  Google Scholar  * 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. Article  CAS  Google Scholar  * 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. CAS  PubMed 

Google Scholar  * 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. Article  CAS  Google Scholar  * 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. Article  CAS  Google Scholar  *

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. Article  CAS  Google Scholar  *

Proescholdt M, Heimann A, Kempski O . Neuroprotection of S (+) ketamine isomer in global forebrain ischemia. _Brain Res_ 2001; 904: 245–51. Article  CAS  Google Scholar  * 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. Article  CAS 

Google Scholar  * 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. Article  CAS  Google Scholar  * Lees GJ . Influence of ketamine on the neuronal death caused by NMDA in the rat hippocampus. _Neuropharmacology_ 1995; 34: 411–7. Article 

CAS  Google Scholar  * 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. Article 

CAS  Google Scholar  * Wu TW, Zeng LH, Wu J, Fung KP . MCI-186: further histochemical and biochemical evidence of neuroprotection. _Life Sci_ 2000; 67: 2387–92. Article  CAS  Google Scholar

  * 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. Article  CAS  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Pharmacology, School of

Medicine, Zhejiang University, Hangzhou, 310058, China Qian Ding, Er-qing Wei, Yan-jun Zhang, Wei-ping Zhang & Zhong Chen Authors * Qian Ding View author publications You can also search

for this author inPubMed Google Scholar * Er-qing Wei View author publications You can also search for this author inPubMed Google Scholar * Yan-jun Zhang View author publications You can

also search for this author inPubMed Google Scholar * Wei-ping Zhang View author publications You can also search for this author inPubMed Google Scholar * Zhong Chen View author

publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Er-qing Wei. ADDITIONAL INFORMATION Project supported by the National Natural

Science Foundation of China (No 30371637). RIGHTS AND PERMISSIONS Reprints 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 Download

citation * Received: 25 April 2006 * Accepted: 26 June 2006 * Issue Date: 01 December 2006 * DOI: https://doi.org/10.1111/j.1745-7254.2006.00438.x SHARE THIS ARTICLE Anyone you share the

following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer

Nature SharedIt content-sharing initiative KEYWORDS * cysteinyl leukotriene receptor * excitotoxicity * _N_-methyl-_D_-aspartate * leukotriene receptor antagonist * pranlukast * NMDA

receptor antagonist * ketamine