NAADP-induced calcium release in sea urchin eggs

Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent ac tivator of Ca2+ release from intracellular stores described. It acts on a m echanism distinct from inositol trisphosphate and ryanodine receptors, the two major Ca2+ release channels characterised. NAADP-gated Ca2+ release cha nnels do not appear to be regulated by Ca2+ and may be better suited for tr iggering Ca2+ signals rather than propagating them. They exhibit a remarkab le pharmacology for a putative intracellular Ca2+ release channel in that t hey are selectively blocked by potassium and L-type Ca2+ channel antagonist s. Furthermore, in contrast to microsomal Ca2+ stores expressing IP(3)Rs an d RyRs, those sensitive to NAADP are thapsigargin-insensitive, suggesting t hat they may be expressed on a different part of the endoplasmic reticulum. Perhaps the most unusual feature of the NAADP-gated Ca2+ release mechanism s is its inactivation properties. Unlike the mechanisms regulated by IP3 an d cADPR in sea urchin eggs which after induction of Ca2+ release appear to become refractory to subsequent activation, very low concentrations of NAAD P are able to inactivate NAADP-induced Ca2+ release fully at concentrations well below those required to activate Ca2+ release. The mechanism and phys iological significance of this most unusual desensitisation phenomenon are unclear. More recently, NAADP has been shown to mobilise Ca2+ in ascidian o ocytes, brain microsomes and pancreatic acinar cells suggesting a more wide spread role in Ca2+ signalling. A possible role for this novel Ca2+ release mechanism in sea urchin egg fertilisation is discussed. (C) 2000 Editions scientifiques et medicales Elsevier SAS.