SPECIFIC MODULATION OF CYCLIC ADP-RIBOSE-INDUCED CA2+ RELEASE BY POLYAMINES

Cyclic ADP-ribose (cADPR) is a potent mediator of Ca2+ mobilization fr om intracellular stores in sea urchin eggs. However, the regulation of the cADPR-induced Ca2+ release system is not yet fully elucidated. We now report that spermine and related polyamines, in physiological con centrations, were able to inhibit the Ca2+ release induced by cADPR in sea urchin egg homogenate bioassays, as measured using the Ca2+ indic ator flue 3, but had no effect on the Ca2+ release induced by D-myo-in ositol 1,4,5-trisphosphate (IP3) or by nicotinate adenine dinucleotide phosphate (NAADP). Spermine was a more potent inhibitor of the cADPR- induced Ca2+ release than spermidine and putrescine. Spermine inhibite d not only the release induced by cADPR but also the Ca2+ release indu ced by caffeine and ryanodine. Finally, pretreatment of the sea urchin egg homogenates with caffeine or Sr2+ and Ca2+ prevented the inhibito ry effect of spermine on cADPR-induced Ca2+ release. We propose that p olyamines, which are present in millimolar concentrations in fertilize d eggs, are specific inhibitors of the ryanodine channel and perhaps m ay serve as endogenous regulators of the cADPR-induced Ca2+ release sy stem.