title: Functional importance of inositol-1,4,5-triphosphate-induced intracellular Ca2+ mobilization in galanin-induced microglial migration.
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 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 receptor antagonist significantly inhibited GAL-induced migration. GAL-induced Ca(2+) 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 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.
authors.affiliation: Laboratory of Pathophysiology, Graduate School of Pharmaceutical Science, Kyushu University, Fukuoka, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Ifuku
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okuno
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yamakawa
authors.forename: Kyoko
authors.initials: K
authors.lastname: Izumi
authors.forename: Stefanie
authors.initials: S
authors.lastname: Seifert
authors.forename: Helmut
authors.initials: H
authors.lastname: Kettenmann
authors.forename: Mami
authors.initials: M
authors.lastname: Noda
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001920:Bradykinin / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D019004:Galanin / Q000502:physiology*; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000819:agonists / Q000502:physiology*; D007424:Intracellular Fluid / Q000378:metabolism / Q000502:physiology*; D017628:Microglia / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D015544:Inositol 1,4,5-Trisphosphate; D019004:Galanin; D001920:Bradykinin