We investigated the effect of glycolytic pathway intermediaries upon Ca2+ release induced by cyclic ADP-ribose (cADPR), inositol 1',4',5- trisphosphate (IP3), and nicotinate adenine dinucleotide phosphate (NAADP) in sea urchin egg homogenate. Fructose 1,6,-diphosphate (FDP), at concentrations up to 8 mM, did not induce Ca2+ release by itself in sea urchin egg homogenate. However, FDP potentiates Ca2+ release mediated by agonists of the ryanodine channel, such as ryanodine, caffeine, and palmitoyl-CoA. Furthermore, glucose 6-phosphate had similar effects. FDP also potentiates activation of the ryanodine channel mediated by the endogenous nucleotide cADPR. The half-maximal concentration for cADPR-induced Ca2+ release was decreased approximately 3.5 times by addition of 4 mM FDP. The reverse was also true: addition of subthreshold concentrations of cADPR sensitized the homogenates to FDP. The Ca2+ release mediated by FDP in the presence of subthreshold concentrations of cADPR was inhibited by antagonists of the ryanodine channel, such as ruthenium red, and by the cADPR inhibitor 8-Br-cADPR. However, inhibition of Ca2+ release induced by IP3 or NAADP had no effect upon Ca2+ release induced by FDP in the presence of low concentrations of cADPR. Furthermore, FDP had inhibitory effects upon Ca2+ release induced by both IP3 and NAADP. We propose that the state of cellular intermediary metabolism may regulate cellular Ca2+ homeostases by switching preferential effects from one intracellular Ca2+ release channel to another.
ASJC Scopus subject areas
- Molecular Biology