Specific modulation of cyclic adp-ribose induced ca2+ release by
polyamines.
Chini, Eduardo Nunes, Kelly W. Beers, Claudia C. S. Chini, and Thomas
P. Dousa.
Nephrology Research Unit, Division of Nephrology and Departments of
Physiology and Internal Medicine, Mayo Clinic and Foundation,
Rochester, MN
APStracts 2:0192C, 1995.
Cyclic ADP-ribose (cADPR) is a potent mediator of calcium mobilization
from intracellular stores in sea urchin eggs. However, the regulation
of the cADPR-induced Ca2+ release system are 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 homogenates bioassay, as measured
using the Ca2+ indicator Fluo-3, but had no effect on the Ca2+
release induced by inositol 1,4,5-trisphosphate (IP3) or by
nicotinate adenine dinucleotide phosphate (NAADP). Spermine was 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, pre-treatment of the sea urchin egg homogenates with
caffeine or strontium and calcium prevent the inhibitory effect of
spermine upon 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.
Received 31 January 1995; accepted in final form 4 May 1995.
APS Manuscript Number C59-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 16 May 1995.