Specific modulation of cyclic ADP-ribose-induced Ca2+ release by polyamines.
Cyclic ADP-ribose (cADPR) is a potent mediator of Ca2+ mobilization from 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 concentrations, were able to inhibit the Ca2+ release induced by cADPR in sea urchin egg homogenate bioassays, as measured using the Ca2+ indicator fluo 3, but had no effect on the Ca2+ release induced by D-myo-inositol 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 inhibited not only the release induced by cADPR but also the Ca2+ release induced by caffeine and ryanodine. Finally, pretreatment of the sea urchin egg homogenates with caffeine or Sr2+ and Ca2+ prevented the inhibitory effect of spermine on cADPR-induced Ca2+ release. We propose that polyamines, which are present in millimolar concentrations in fertilized eggs, are specific inhibitors of the ryanodine channel and perhaps may serve as endogenous regulators of the cADPR-induced Ca2+ release system.
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D036563:Cyclic ADP-Ribose; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D009249:NADP / Q000031:analogs & derivatives / Q000494:pharmacology; D010063:Ovum / Q000378:metabolism; D011073:Polyamines / Q000494:pharmacology*; D012433:Ryanodine / Q000494:pharmacology; D012617:Sea Urchins / Q000378:metabolism; D013096:Spermine / Q000494:pharmacology
D011073:Polyamines; D036563:Cyclic ADP-Ribose; D012433:Ryanodine; D000246:Adenosine Diphosphate Ribose; D013096:Spermine; D002110:Caffeine; D009249:NADP; C024376:NAADP; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium