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

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.

[1]  T. Standiford,et al.  Interleukin-36γ and IL-36 receptor signaling mediate impaired host immunity and lung injury in cytotoxic Pseudomonas aeruginosa pulmonary infection: Role of prostaglandin E2 , 2017, PLoS pathogens.

[2]  Yan Zhao,et al.  Dramatic increases in blood glutamate concentrations are closely related to traumatic brain injury-induced acute lung injury , 2017, Scientific Reports.

[3]  I. Adcock,et al.  Conjugated Alpha-Alumina nanoparticle with vasoactive intestinal peptide as a Nano-drug in treatment of allergic asthma in mice. , 2016, European journal of pharmacology.

[4]  S. Yue,et al.  N-methyl-D-aspartate receptor activation mediates lung fibroblast proliferation and differentiation in hyperoxia-induced chronic lung disease in newborn rats , 2016, Respiratory Research.

[5]  Dao-xin Wang,et al.  Rapamycin attenuates acute lung injury induced by LPS through inhibition of Th17 cell proliferation in mice , 2016, Scientific Reports.

[6]  Guojun Wu,et al.  Expression of Nodal on Bronchial Epithelial Cells Influenced by Lung Microbes Through DNA Methylation Modulates the Differentiation of T-Helper Cells , 2015, Cellular Physiology and Biochemistry.

[7]  M. Ma,et al.  Blockade of the N-Methyl-D-Aspartate Glutamate Receptor Ameliorates Lipopolysaccharide-Induced Renal Insufficiency , 2015, PloS one.

[8]  P. Hof,et al.  Analysis of synaptic gene expression in the neocortex of primates reveals evolutionary changes in glutamatergic neurotransmission. , 2015, Cerebral cortex.

[9]  Wei Liu,et al.  NMDA Receptor Antagonist Attenuates Bleomycin-Induced Acute Lung Injury , 2015, PloS one.

[10]  Y. Donati,et al.  Prevention of hyperoxia-induced bronchial hyperreactivity by sildenafil and vasoactive intestinal peptide: impact of preserved lung function and structure , 2014, Respiratory Research.

[11]  M. Muñoz,et al.  Involvement of substance P and the NK-1 receptor in human pathology , 2014, Amino Acids.

[12]  J. Roder,et al.  α7nAchR/NMDAR coupling affects NMDAR function and object recognition , 2013, Molecular Brain.

[13]  J. Palermo-neto,et al.  Effects of MK-801 and amphetamine treatments on allergic lung inflammatory response in mice. , 2013, International immunopharmacology.

[14]  M. Muñoz,et al.  The substance P/neurokinin-1 receptor system in lung cancer: Focus on the antitumor action of neurokinin-1 receptor antagonists , 2012, Peptides.

[15]  P. MacAry,et al.  Hydrogen Sulfide and Neurogenic Inflammation in Polymicrobial Sepsis: Involvement of Substance P and ERK-NF-κB Signaling , 2011, PloS one.

[16]  J. L. Rosa,et al.  Treatment with N-methyl-D-aspartate receptor antagonist (MK-801) protects against oxidative stress in lipopolysaccharide-induced acute lung injury in the rat. , 2011, International immunopharmacology.

[17]  Xue Xin-dong.  Protective effect of Losartan in hyperoxia-induced chronic lung disease in newborn rats , 2011 .

[18]  T. Heyming,et al.  Stimulation of lateral hypothalamic AMPA receptors may induce feeding in rats , 2010, Brain Research.

[19]  Shui-ping Liu,et al.  Infection with respiratory syncytial virus alters peptidergic innervation in the lower airways of guinea‐pigs , 2008, Experimental physiology.

[20]  R. Hargreaves,et al.  Localization of N-methyl-d-aspartate NR2B subunits on primary sensory neurons that give rise to small-caliber sciatic nerve fibers in rats , 2000, Neuroscience.