Cell-permeant small-molecule modulators of NAADP-mediated Ca2+ release.
Chem Biol
; 13(6): 659-65, 2006 Jun.
Article
in En
| MEDLINE
| ID: mdl-16793523
ABSTRACT
Nicotinic acid adenine dinucleotide phosphate (NAADP, 1) is the most potent intracellular Ca2+ mobilizing agent in important mammalian cells and tissues, yet the identity of the NAADP receptor is elusive. Significantly, the coenzyme NADP is completely inactive in this respect. Current studies are restricted by the paucity of any chemical probes beyond NAADP itself, and importantly, none is cell permeant. We report simple nicotinic acid-derived pyridinium analogs as low molecular weight compounds that (1) inhibit Ca2+ release via the NAADP receptor (IC50 approximately 15 microM - 1 mM), (2) compete with NAADP binding, (3) cross the cell membrane of sea urchin eggs to inhibit NAADP-evoked Ca2+ release, and (4) selectively ablate NAADP-dependent Ca2+ oscillations induced by the external gastric peptide hormone agonist cholecystokinin (CCK) in murine pancreatic acinar cells.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyridines
/
Cell Membrane Permeability
/
Calcium
/
NADP
Limits:
Animals
Language:
En
Journal:
Chem Biol
Journal subject:
BIOLOGIA
/
BIOQUIMICA
/
QUIMICA
Year:
2006
Document type:
Article
Affiliation country: