Nicotinic acid adenine dinucleotide phosphate: A new Ca²⁺ releasing agent in kidney

Nicotinic acid adenine dinucleotide phosphate (NAADP), a molecule derived from β-NADP, has been shown to trigger Ca²⁺ release from intracellular stores of invertebrate eggs and mammalian cell microsomes. NAADP-induced Ca²⁺ release occurs through a mechanism distinct from that of inositol-1,4,5-trisphosphate- or cyclic ADP-ribose-elicited Ca²⁺ release. This study investigated whether NAADP can be synthesized in rat kidney. Extracts from glomeruli, mesangial cells, and papilla have high NAADP synthetic capacities. Conversely, synthesis of NAADP in kidney cortex was almost undetectable. Furthermore, 9-cis-retinoic acid significantly upregulated NAADP synthesis in mesangial cells. Authenticity of NAADP biosynthesis in glomeruli was affirmed by HPLC analysis. NAADP stimulated Ca²⁺ release from mesangial cell microsomes through a pathway distinct from that of inositol-1,4,5-trisphosphate or cyclic ADP-ribose. NAADP-triggered Ca²⁺ release may play an important role in regulation of renal function.