Functional importance of inositol-1,4,5-triphosphate-induced intracellular Ca2+ mobilization in galanin-induced microglial migration

Masataka Ifuku, Yuko Okuno, Yukiko Yamakawa, Kyoko Izumi, Stefanie Seifert, Helmut Kettenmann, Mami Noda

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Galanin (GAL) is a neuropeptide which is up-regulated following neuronal axotomy or inflammation. One subtype of GAL receptor (GalR2) is reported to be expressed in the brain's immune cell population, microglia. In the present study, we investigated the effect of GAL on microglial migration and compared the mechanism with that of bradykinin (BK). GAL significantly increased the migration of rat cultured microglia at 0.1 pM. The GAL-induced signal cascade was partly similar to that induced by BK. It was not dependent on G i/o protein but involved activation of protein kinase C, phosphoinositide 3-kinase and Ca2+-dependent K+ channels. However, reverse-mode activation of the Na+/Ca2+-exchanger 1 was not involved in GAL-induced microglial migration, unlike BK-induced migration. Likewise, nominally-free extracellular Ca2+ inhibited BK-induced migration but not GAL-induced migration. An inositol-1,4,5- triphosphate receptor antagonist significantly inhibited GAL-induced migration. GAL-induced Ca2+ signaling did not induce nitric oxide synthase expression, but up-regulated class II major histocompatibility complex expression. These results indicate that activation of inositol-1,4,5- triphosphate receptor and increase in intracellular Ca2+ are important for GAL-induced migration and immunoreactivity in microglia. The differences in down-stream signal transduction induced by GAL and BK suggest that GAL and BK may control distinct microglial functions under pathological conditions.

Original languageEnglish
Pages (from-to)61-70
Number of pages10
JournalJournal of Neurochemistry
Volume117
Issue number1
DOIs
Publication statusPublished - Apr 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

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