Widespread distribution of binding sites for the novel Ca2+-mobilizing messenger, nicotinic acid adenine dinucleotide phosphate, in the brain

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca2+-mobi lizing agent in invertebrate eggs that has recently been shown to be active in certain mammalian and plant systems, Little, however, is known concerni ng the properties of putative NAADP receptors. Here, for the first time, we report binding sites for NAADP in brain. In contrast to sea urchin egg hom ogenates, [P-32]NAADP bound reversibly to multiple sites in brain membranes . The rank order of potency of NAADP, 2',3'-cyclic NAADP and 3'-NAADP in di splacing [P-32]NAADP was, however, the same in the two systems and in agree ment with their ability to mobilize Ca2+ from homogenates, These data indic ate that [P-32]NAADP likely binds to receptors mediating Ca2+ mobilization. Autoradiography revealed striking heterogeneity in the distribution of [P- 32]NAADP binding sites throughout the brain. Our data strongly support a ro le for NAADP-induced Ca2+ signaling in the brain.