Extracellular application of nicotinic acid adenine dinucleotide phosphate induces Ca2+ signaling in astrocytes in situ.
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.
Heidemann
Antje C
AC
Max-Delbrück-Center for Molecular Medicine, Cellular Neuroscience, 10 Robert-Rössle-Strasse, Berlin D-13092, Germany.
Schipke
Carola G
CG
Kettenmann
Helmut
H
D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis; D000241:Adenosine / Q000737:chemistry; D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D002490:Central Nervous System / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D017630:Connexins / Q000737:chemistry; D007150:Immunohistochemistry; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009249:NADP / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
D017630:Connexins; D009249:NADP; C024376:NAADP; D015544:Inositol 1,4,5-Trisphosphate; D051997:ADP-ribosyl Cyclase 1; D000241:Adenosine; D002118:Calcium