Nicotinic acid adenine dinucleotide phosphate (NAADP) has been shown to be a powerful Ca2+ release agent in numerous systems, including echinoderms, plants. and mammalian cells. NAADP has been shown to release Ca2+ via a separate mechanism to IP3, and ryanodine receptors. and specific binding sites have recently been characterised. However. functional studies have shown that there is a functional interplay between the NAADP-sensitive mechanism and the other two. In particular. it appears that activation of the NAADP receptor might act as a trigger to facilitate responses from IP3 and ryanodine receptors. To further characterise this interplay. we have investigated the effects of luminal and cytosolic Ca2+ on the NAADP receptor in sea urchin egg homogenates. We report that neither cytosolic nor luminal Ca2+ appears to influence NAADP binding. Conversely, emptying of stores significantly amplifies NAADP-induced fractional Ca2+-release. providing a mechanism of self-adjustment independent of store loading. (C) 2002 Elsevier Science (USA). All rights reserved.