Biochem/physiol Actions

NAADP (nicotinic acid adenine dinucleotide phosphate) has recently been recognized as a crucial Ca²⁺-releasing second messenger in several mammalian tissues including pancreatic, brain and cardiac. Ned-19 is a potent inhibitor of NAADP action. It is a selective blocker of cellular NAADP-induced Ca²⁺-release and can fluorescently label NAADP receptors. Ned-19 blocks NAADP signaling at nanomolar concentrations. In intact cells, Ned-19 blocked NAADP signaling and fluorescently labeled NAADP receptors.The trans-Ned-19 is more potent than the cis form in regard to both inhibition of Ca²⁺ release (IC₅₀ of 6 nM versus 800 nM) and [32P]NAADP binding (IC₅₀ of 0.4 nM versus 15 µM).