Nicotinic acid-adenine dinucleotide phosphate (NAADP) elicits specific microsomal Ca2+ release from mammalian cells

Nicotinic acid-adenine dinucleotide phosphate (NAADP), a molecule derived f rom beta -NADP. has been shown to promote intracellular calcium release in sea urchin eggs. However, there is little information regarding the role of NAADP in the regulation of intracellular calcium fluxes in mammalian cells . We found recently that several mammalian tissues have a high capacity for NAADP synthesis, as assessed by sea urchin egg bioassay. To determine the functional significance of NAADP production by mammalian tissues, we sought to determine whether NAADP is capable of inducing calcium release from mic rosomes prepared from cultured cells. We found that NAADP, but not beta -NA DP. activates a specific microsomal calcium release system in mesangial cel ls isolated from rat kidney: NAADP was without effect in renal tubular epit helial cells. NAADP-induced calcium release is not affected by inhibitors o f the inositol 1,4,5-trisphosphate or ryanodine channels. However, NAADP-el icited calcium release was inhibited by L-type calcium channel blockers and by alkaline phosphatase treatment of NAADP. NAADP also promotes specific m icrosomal calcium release in rat vascular smooth muscle cells, cardiac myoc ytes, fibroblasts and a human leukaemia cell line, indicating that the capa city for NAADP-induced calcium release is widespread in mammalian cells. We propose that NAADP may be an important regulator of intracellular calcium in many mammalian tissues.