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(Received for publication, July 10, 1996, and in revised form, October 30, 1996)
From the Department of Pharmacology, Three endogenous molecules have now been shown to
release Ca2+ in the sea urchin egg: inositol
trisphosphate (InsP3), cyclic adenosine 5
-diphosphate
ribose (cADPR), and nicotinic acid adenine dinucleotide phosphate
(NAADP), a derivative of NADP. While the mechanism through which the
first two molecules are able to release Ca2+ is established
and well characterized with InsP3 and cADPR-activating InsP3 and ryanodine receptors, respectively, the newly
described NAADP has been shown to release Ca2+ via an
entirely different mechanism. The most striking feature of this novel
Ca2+ release mechanism is its inactivation, since
subthreshold concentrations of NAADP are able to fully and irreversibly
desensitize the channel. In the present study we have investigated the
fast kinetics of activation and inactivation of NAADP-induced
Ca2+ release. NAADP was found to release Ca2+
in a biphasic manner, and such release was preceded by a pronounced latent period, which was inversely dependent on concentration. Moreover, the kinetic features of NAADP-induced Ca2+
release were not altered by pretreatment with low concentrations of
NAADP, although the extent of Ca2+ release was greatly
affected. Our data suggest that the inactivation of NAADP-induced
Ca2+ release is an all-or-none phenomenon, and while some
receptors have been fully inactivated, those that remain sensitive to
NAADP do so without any change in kinetic features.
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