Functional importance of inositol-1,4,5-triphosphate-induced intracellular Ca(2+) mobilization in galanin-induced microglial migration

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Item Type:	Article
Title:	Functional importance of inositol-1,4,5-triphosphate-induced intracellular Ca(2+) mobilization in galanin-induced microglial migration
Creators Name:	Ifuku, M., Okuno, Y., Yamakawa, Y., Izumi, K., Seifert, S., Kettenmann, H. and Noda, M.
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 Ca(2+) -dependent K(+) channels. However, reverse-mode activation of the Na(+) /Ca(2+) -exchanger 1 (NCX1) was not involved in GAL-induced microglial migration, unlike BK-induced migration. Likewise, nominally-free extracellular Ca(2+) inhibited BK-induced migration but not GAL-induced migration. An inositol-1,4,5-triphosphate (IP(3) ) receptor antagonist significantly inhibited GAL-induced migration. GAL-induced Ca(2+) signaling did not induce nitric oxide synthase (iNOS) expression, but up-regulated MHC class II expression. These results indicate that activation of IP(3) receptor and increase in intracellular Ca(2+) 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.
Keywords:	Galanin, Bradykinin, Microglia, Migration, Inositol-1,4,5-Triphosphate, MHC Class II, Animals, Rats
Source:	Journal of Neurochemistry
ISSN:	0022-3042
Publisher:	Wiley-Blackwell
Volume:	117
Number:	1
Page Range:	61-70
Date:	April 2011
Official Publication:	https://doi.org/10.1111/j.1471-4159.2011.07176.x
PubMed:	View item in PubMed

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