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+-mobilizing agent in invertebrate eggs that has recently been shown to be active in certain mammalian and plant systems. Little, however, is known concerning 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 homogenates, [32P]NAADP bound reversibly to multiple sites in brain membranes. The rank order of potency of NAADP, 2′,3′-cyclic NAADP and 3′-NAADP in displacing [32P]NAADP was, however, the same in the two systems and in agreement with their ability to mobilize Ca2+ from homogenates. These data indicate that [32P]NAADP likely binds to receptors mediating Ca2+ mobilization. Autoradiography revealed striking heterogeneity in the distribution of [32P]NAADP binding sites throughout the brain. Our data strongly support a role for NAADP-induced Ca2+ signaling in the brain.