Specific modulation of cyclic ADP-ribose-induced Ca2+ release by polyamines

Am J Physiol. 1995 Oct;269(4 Pt 1):C1042-7. doi: 10.1152/ajpcell.1995.269.4.C1042.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Diphosphate Ribose / analogs & derivatives*
  • Adenosine Diphosphate Ribose / pharmacology
  • Animals
  • Caffeine / pharmacology
  • Calcium / metabolism*
  • Cyclic ADP-Ribose
  • Inositol 1,4,5-Trisphosphate / pharmacology
  • NADP / analogs & derivatives
  • NADP / pharmacology
  • Ovum / metabolism
  • Polyamines / pharmacology*
  • Ryanodine / pharmacology
  • Sea Urchins / metabolism
  • Spermine / pharmacology


  • Polyamines
  • Cyclic ADP-Ribose
  • Ryanodine
  • Adenosine Diphosphate Ribose
  • Spermine
  • Caffeine
  • NADP
  • Inositol 1,4,5-Trisphosphate
  • Calcium