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NAADP+ is an agonist of the human P2Y11 purinergic receptor.
- Source :
-
Cell calcium [Cell Calcium] 2008 Apr; Vol. 43 (4), pp. 344-55. Date of Electronic Publication: 2007 Aug 17. - Publication Year :
- 2008
-
Abstract
- Nicotinic acid adenine dinucleotide phosphate (NAADP+) is an intracellular second messenger releasing Ca2+ from intracellular stores in different cell types. In addition, it is also active in triggering [Ca2+](i) increase when applied extracellularly and various underlying mechanisms have been proposed. Here, we used hP2Y(11)-transfected 1321N1 astrocytoma cells to unequivocally establish whether extracellular NAADP+ is an agonist of the P2Y(11) receptor, as previously reported for beta-NAD+ [I. Moreschi, S. Bruzzone, R.A. Nicholas, et al., Extracellular NAD+ is an agonist of the human P2Y11 purinergic receptor in human granulocytes, J. Biol. Chem. 281 (2006) 31419-31429]. Extracellular NAADP+ triggered a concentration-dependent two-step elevation of [Ca2+](i) in 1321N1-hP2Y(11) cells, but not in wild-type 1321N1 cells, secondary to the intracellular production of IP(3), cAMP and cyclic ADP-ribose (cADPR). Specifically, the transient [Ca2+](i) rise proved to be related to IP(3) overproduction and to consequent Ca2+ mobilization, while the sustained [Ca2+](i) elevation was caused by the cAMP/ADP-ribosyl cyclase (ADPRC)/cADPR signalling cascade and by influx of extracellular Ca2+. In human granulocytes, endogenous P2Y(11) proved to be responsible for the NAADP+-induced cell activation (as demonstrated by the use of NF157, a selective and potent inhibitor of P2Y(11)), unveiling a role of NAADP+ as a pro-inflammatory cytokine. In conclusion, we provide unequivocal evidence for the activation of a member of the P2Y receptor subfamily by NAADP+.
- Subjects :
- Animals
Cell Line
Chemotaxis physiology
Cyclic ADP-Ribose metabolism
Cyclic AMP metabolism
Granulocytes cytology
Granulocytes metabolism
Humans
Inositol 1,4,5-Trisphosphate metabolism
NADP metabolism
Receptors, Purinergic P2 metabolism
Calcium metabolism
NADP analogs & derivatives
Purinergic P2 Receptor Agonists
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0143-4160
- Volume :
- 43
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cell calcium
- Publication Type :
- Academic Journal
- Accession number :
- 17707504
- Full Text :
- https://doi.org/10.1016/j.ceca.2007.06.006