کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1391822 | 983647 | 2006 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Cell-Permeant Small-Molecule Modulators of NAADP-Mediated Ca2+ Release Cell-Permeant Small-Molecule Modulators of NAADP-Mediated Ca2+ Release](/preview/png/1391822.png)
SummaryNicotinic 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 ∼15μM – 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.
Journal: - Volume 13, Issue 6, June 2006, Pages 659–665