Blockade of glutamate receptor ameliorates lipopolysaccharide-induced sepsis through regulation of neuropeptides.

Zhai Zhe,Qiao Wenjuan,Gao Yan,Wang Peng,Liu Xiaowei,Bi Hongyuan

doi:10.1042/bsr20171629

Zhai Zhe, Qiao Wenjuan + Show 4 more

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https://doi.org/10.1042/bsr20171629

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Abstract

Glutamate receptors (N-methyl-d-aspartate receptor (NMDAR)) are expressed mainly in the central nervous system (CNS), but several potentially important exceptions are worth mentioning. Recently, NMDAR, a glutamate receptor, has been reported to be found in the lungs. NMDAR is activated in acute lung injury (ALI). Here, the present experiment was designed to examine whether NMDAR blockade (MK-801) ameliorates ALI through affecting neuropeptides in LPS-induced sepsis animal models. Male Kunming mice were divided into control group, LPS group, control + MK-801 group, and LPS + MK-801 group. Bronchoalveolar lavage fluid (BALF) was collected and evaluated. The lung histological pathology was assayed by immunocytochemistry staining. Western blot was used to measure PGP9.5, substance P (SP), and vasoactive intestinal polypeptide (VIP). Results showed that LPS-induced mice animal models were ameliorated by co-treatment with the MK-801, an uncompetitive NMDAR antagonist. Moreover, the protective effects of MK-801 attributed to the increased secretion of VIP and decreased secretion of SP. The results of the present study indicated that the blockade of NMDAR may represent a promising therapeutic strategy for the treatment of sepsis-associated ALI through regulation of neuropeptides.

Highlights

Glutamate (Glu) is the main excitatory neurotransmitter which acts on glutamate receptors in the central nervous system (CNS) but overactivation of these receptors can cause several damages to neural cells including death
Glutamate receptors are divided into two categories based on the mechanism by which their activation gives rise to a post-synaptic current: one for the ionotropic receptors, including: N-methyl-d-aspartate receptor (NMDAR), kainic acid receptor (KAR), and α-amino-3 hydroxy-5 methyl isoxazole-4 receptor (AMPAR), which are coupled with ion channel to form the receptor channel complex, mediating a fast signal transmission; the other belongs to a class of metabotropic receptors, which are coupled with membrane, produces a slow physiological response [4]
Numerous studies have shown that glutamate and its NMDAR play an important role in cell injury

Summary

Introduction

Glutamate (Glu) is the main excitatory neurotransmitter which acts on glutamate receptors in the central nervous system (CNS) but overactivation of these receptors can cause several damages to neural cells including death. Recent studies show that the glutamate agonist N-methyl-d-aspartate (NMDA) can trigger acute lung injury (ALI). ALI is a direct and indirect injury to alveolar epithelial cells and capillary endothelial cell, causing diffuse pulmonary interstitial and alveolar edema and acute hypoxic respiration failure. Numerous studies have shown that glutamate and its NMDAR play an important role in cell injury. NMDAR has been the focus of much attention because of its implication in cell injury and death in acute conditions [5].

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