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Extracellular application of NAADP+ induces Ca2+ signaling in astrocytes in situ

Item Type:Article
Title:Extracellular application of NAADP+ induces Ca2+ signaling in astrocytes in situ
Creators Name:Heidemann, A.C. and Schipke, C.G. and Kettenmann, H.
Abstract:Nicotinic acid adenine dinucleotide phosphate (NAADP+) has been identified as a novel second messenger triggering Ca2+ release from intracellular stores. Here we report that murine cortical astrocytes in culture and in acute slices respond with transient intracellular Ca2+ increases to extracellularly applied NAADP+ and express the NAADP+-producing enzyme CD38. The Ca2+ transients triggered by NAADP+ occurred with an average delay of 35 s as compared with ATP-triggered Ca2+ signaling, suggesting that NAADP+ may have to enter the cell to act. Blockage of connexin hemichannels (a possible entry route for NAADP+ into the cell) reduced the number of astrocytes responding to NAADP+. Disruption of lysosomes as the suggested site of NAADP+ receptors reduced the number of astrocytes responding to NAADP+ strongly. The NAADP+-triggered Ca2+ signal also depended on intact endoplasmic reticulum Ca2+ stores linked to activation of inositol 1,4,5-trisphosphate receptors and on the activity of voltage-gated Ca2+ channels. Adenosine receptor-mediated signaling contributes to the NAADP+-evoked signal, since it is strongly reduced by the adenosine receptor blocker CGS-15943. Moreover, NAADP+ triggered responses in all other cell types (cultured cerebellar neurons, microglia, and oligodendrocytes) of the central nervous system.
Keywords:Adenosine, Astrocytes, Biological Models, Calcium, CD38 Antigens, Central Nervous System, Cerebellum, Connexins, Immunohistochemistry, Inositol 1,4,5-Trisphosphate, Lysosomes, NADP, Neurons, Oligodendroglia, Signal Transduction, Time Factors, Tumor Cell Line, Animals, Mice
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:280
Number:42
Page Range:35630-35640
Date:21 October 2005
Official Publication:https://doi.org/10.1074/jbc.M507338200
PubMed:View item in PubMed

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