Lysophosphatidic acid activates satellite glia cells and Schwann cells.
Glia
; 67(5): 999-1012, 2019 05.
Article
em En
| MEDLINE
| ID: mdl-30637823
ABSTRACT
Pruritus is a common and disabling symptom in patients with hepatobiliary disorders, particularly in those with cholestatic features. Serum levels of lysophosphatidic acid (LPA) and its forming enzyme autotaxin were increased in patients suffering from hepatic pruritus, correlated with itch severity and response to treatment. Here we show that in a culture of dorsal root ganglia LPA 181 surprisingly activated a large fraction of satellite glia cells, and responses to LPA 181 correlated inversely with responses to neuronal expressed transient receptor potential channels. LPA 181 caused only a marginal activation of heterologously expressed TRPV1, and responses in dorsal root ganglion cultures from TRPV1-deficient mice were similar to controls. LPA 181 desensitized subsequent responsiveness to chloroquine and TGR5 agonist INT-777. The LPA 181-induced increase in cytoplasmatic calcium stems from the endoplasmatic reticulum. LPA receptor expression in dorsal root ganglia and Schwann cells, LPAR1 immunohistochemistry, and pharmacological results indicate a signaling pathway through LPA receptor 1. Peripheral rat Schwann cells, which are of glial lineage as the satellite glia cells, were also responsive to LPA 181. Summarizing, LPA 181 primarily activates rather glial cells than neurons, which may subsequently modulate neuronal responsiveness and sensory sensations such as itch and pain.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células de Schwann
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Lisofosfolipídeos
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Regulação da Expressão Gênica
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Neuroglia
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Células Satélites Perineuronais
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article