Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Proteínas do Líquido Cefalorraquidiano/análise , Proteínas do Tecido Nervoso/análise , Proteínas do Tecido Nervoso/líquido cefalorraquidiano , Doença de Parkinson/líquido cefalorraquidiano , Proteômica/métodos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/fisiopatologia , Apolipoproteínas E/análise , Apolipoproteínas E/líquido cefalorraquidiano , Biomarcadores/análise , Biomarcadores/líquido cefalorraquidiano , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Complemento C4a/análise , Complemento C4a/líquido cefalorraquidiano , Diagnóstico Diferencial , Proteínas do Olho/análise , Proteínas do Olho/líquido cefalorraquidiano , Humanos , Complexos Multienzimáticos/análise , Complexos Multienzimáticos/líquido cefalorraquidiano , Fatores de Crescimento Neural/análise , Fatores de Crescimento Neural/líquido cefalorraquidiano , Doença de Parkinson/diagnóstico , Doença de Parkinson/fisiopatologia , Fosfodiesterase I/análise , Fosfodiesterase I/líquido cefalorraquidiano , Diester Fosfórico Hidrolases , Valor Preditivo dos Testes , Pirofosfatases/análise , Pirofosfatases/líquido cefalorraquidiano , Serpinas/análise , Serpinas/líquido cefalorraquidiano , Superóxido Dismutase/análise , Superóxido Dismutase/líquido cefalorraquidiano , Superóxido Dismutase-1 , Regulação para Cima/fisiologiaAssuntos
Técnicas Imunoenzimáticas/métodos , Complexos Multienzimáticos/líquido cefalorraquidiano , Complexos Multienzimáticos/imunologia , Fosfodiesterase I/líquido cefalorraquidiano , Fosfodiesterase I/imunologia , Pirofosfatases/líquido cefalorraquidiano , Pirofosfatases/imunologia , Humanos , Diester Fosfórico HidrolasesRESUMO
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.