Nicotinic acid adenine dinucleotide phosphate potentiates neurite outgrowth.
Ca(2+) regulates a spectrum of cellular processes including many aspects of neuronal function. Ca(2+)-sensitive events such as neurite extension and axonal guidance are driven by Ca(2+) signals that are precisely organized in both time and space. These complex cues result from both Ca(2+) influx across the plasma membrane and the mobilization of intracellular Ca(2+) stores. In the present study, using rat cortical neurons, we have examined the effects of the novel intracellular Ca(2+)-mobilizing messenger nicotinic acid adenine dinucleotide phosphate (NAADP) on neurite length and cytosolic Ca(2+) levels. We show that NAADP potentiates neurite extension in response to serum and nerve growth factor and stimulates increases in cytosolic Ca(2+) from bafilomycin-sensitive Ca(2+) stores. Simultaneous blockade of inositol trisphosphate and ryanodine receptors abolished the effects of NAADP on neurite length and reduced the magnitude of NAADP-mediated Ca(2+) signals. This is the first report demonstrating functional NAADP receptors in a mammalian neuron. Interplay between NAADP receptors and more established intracellular Ca(2+) channels may therefore play important signaling roles in the nervous system.
Brailoiu
Eugen
E
Department of Pharmacology, Temple University Medical School, Philadelphia, PA 19140, USA.
Hoard
Jennifer L
JL
Filipeanu
Catalin M
CM
Brailoiu
G Cristina
GC
Dun
Siok L
SL
Patel
Sandip
S
Dun
Nae J
NJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D049108:Cell Enlargement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects*; D002478:Cells, Cultured; D007295:Inositol Phosphates / Q000037:antagonists & inhibitors / Q000378:metabolism; D008081:Liposomes; D047028:Macrocyclic Compounds; D018942:Macrolides / Q000494:pharmacology; D009249:NADP / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects* / Q000502:physiology*; D010080:Oxazoles / Q000494:pharmacology; D051381:Rats; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
D007295:Inositol Phosphates; D008081:Liposomes; D047028:Macrocyclic Compounds; D018942:Macrolides; D010080:Oxazoles; D019837:Ryanodine Receptor Calcium Release Channel; C108644:xestospongin A; D012433:Ryanodine; D009249:NADP; C024376:NAADP; D019284:Thapsigargin; C040929:bafilomycin A1; D002118:Calcium