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

Author:

Chini E. N.1,Beers K. W.1,Chini C. C.1,Dousa T. P.1

Affiliation:

1. Department of Physiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.

Abstract

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.

Publisher

American Physiological Society

Subject

Cell Biology,Physiology

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