Effect of luminal and extravesicular Ca2+ on NAADP binding and release properties.
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.
Department of Pharmacology, Tennis Court Road, Cambridge, UK.
Judit
J
Bak
Richard A
RA
Billington
Armando A
AA
Genazzani
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D009249:NADP / Q000031:analogs & derivatives* / Q000378:metabolism*; D011485:Protein Binding; D012617:Sea Urchins; D013997:Time Factors
D009249:NADP; C024376:NAADP; D015759:Ionomycin; D002118:Calcium