|Simultaneous stimulation of spinal NK1 and NMDA receptors produces LPC which undergoes ATX-mediated conversion to LPA, an initiator of neuropathic pain.|
|PMID: 19014389 Owner: NLM Status: MEDLINE|
|We previously reported that nerve injury-induced neuropathic pain and its underlying mechanisms are initiated by lysophosphatidic acid. In the present study, by measuring cell-rounding in a biological assay using lysophosphatidic acid 1 receptor-expressing B103 cells, we evaluated the molecular mechanism underlying lysophosphatidic acid biosynthesis following intense stimulation of primary afferents. Lysophosphatidic acid production was induced by treatment of spinal cord slices with capsaicin (10 microM), an intense stimulator of primary afferents, in the presence of recombinant autotaxin, but not in its absence. Lysophosphatidic acid was also induced by combination treatment of slices with high doses (10 and 30 microM) of substance P and NMDA, but not by other combinations of substance P, NMDA, calcitonin gene-related peptide and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (30 microM each) in the presence of recombinant autotaxin. We also found that following neurokinin 1 and NMDA receptor activation, activation of both cytosolic phospholipase A(2) and calcium-independent intracellular phospholipase A(2) signalling pathways through protein kinase C and mitogen-activated protein/extracellular signal-regulated kinase activation and intracellular calcium elevation were required for lysophosphatidic acid production. These findings suggest that simultaneous intense stimulation of neurokinin 1 and NMDA receptors in the spinal dorsal horn triggers lysophosphatidic acid production from lysophosphatidylcholine through extracellular autotaxin.|
|Makoto Inoue; Lin Ma; Junken Aoki; Hiroshi Ueda|
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|Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't Date: 2008-11-05|
|Title: Journal of neurochemistry Volume: 107 ISSN: 1471-4159 ISO Abbreviation: J. Neurochem. Publication Date: 2008 Dec|
|Created Date: 2008-12-19 Completed Date: 2009-04-09 Revised Date: 2011-11-07|
Medline Journal Info:
|Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: England|
|Languages: eng Pagination: 1556-65 Citation Subset: IM|
|Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|
|APA/MLA Format Download EndNote Download BibTex|
Analysis of Variance
Calcitonin Gene-Related Peptide / pharmacology
Capsaicin / pharmacology
Cell Line, Transformed
Dose-Response Relationship, Drug
Excitatory Amino Acid Agonists / pharmacology
Lysophosphatidylcholines / metabolism*
Lysophospholipids / metabolism*, pharmacology
Multienzyme Complexes / cerebrospinal fluid, metabolism*
N-Methylaspartate / pharmacology
Phosphodiesterase I / cerebrospinal fluid, metabolism*
Phospholipases A2 / metabolism
Protein Kinase C / metabolism
Pyrophosphatases / cerebrospinal fluid, metabolism*
Receptors, Lysophosphatidic Acid / metabolism
Receptors, N-Methyl-D-Aspartate / physiology*
Receptors, Neurokinin-1 / physiology*
Signal Transduction / drug effects, physiology
Spinal Cord / drug effects, metabolism*
Substance P / pharmacology
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology
|0/Excitatory Amino Acid Agonists; 0/Lysophosphatidylcholines; 0/Lysophospholipids; 0/Multienzyme Complexes; 0/Receptors, Lysophosphatidic Acid; 0/Receptors, N-Methyl-D-Aspartate; 0/Receptors, Neurokinin-1; 22002-87-5/lysophosphatidic acid; 33507-63-0/Substance P; 404-86-4/Capsaicin; 6384-92-5/N-Methylaspartate; 77521-29-0/alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; 83652-28-2/Calcitonin Gene-Related Peptide; EC 18.104.22.168/Protein Kinase C; EC 22.214.171.124/Phospholipases A2; EC 126.96.36.199/Phosphodiesterase I; EC 188.8.131.52/alkylglycerophosphoethanolamine phosphodiesterase; EC 3.6.1.-/Pyrophosphatases|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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