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J. Biol. Chem., Vol. 275, Issue 49, 38687-38692, December 8, 2000
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From the University of Oxford, Department of Pharmacology,
Mansfield Road, Oxford OX1 3QT, United Kingdom
Intracellular Ca2+ is able to
control numerous cellular responses through complex spatiotemporal
organization. Ca2+ waves mediated by inositol trisphosphate
or ryanodine receptors propagate by Ca2+-induced
Ca2+ release and therefore do not have an absolute
requirement for a gradient in either inositol trisphosphate or cyclic
ADP-ribose, respectively. In contrast, we report that although
Ca2+ increases induced by nicotinic acid adenine
dinucleotide phosphate (NAADP) are amplified by
Ca2+-induced Ca2+ release locally,
Ca2+ waves mediated by NAADP have an absolute requirement
for an NAADP gradient. If NAADP is increased such that its
concentration is spatially uniform in one region of an egg, the
Ca2+ increase occurs simultaneously throughout this area,
and only where there is diffusion out of this area to establish an
NAADP gradient is there a Ca2+ wave. A local increase in
NAADP results in a Ca2+ increase that spreads by NAADP
diffusion. NAADP diffusion is restricted at low but not high
concentrations of NAADP, indicating that NAADP diffusion is strongly
influenced by binding to immobile and saturable sites, probably the
NAADP receptor itself. Thus, the range of action of NAADP can be tuned
by its concentration from that of a local messenger, like
Ca2+, to that of a global messenger, like IP3
or cyclic ADP-ribose.
Spatial Control of Ca2+ Signaling by Nicotinic Acid
Adenine Dinucleotide Phosphate Diffusion and Gradients*
and
*
This work was supported by the Wellcome Trust.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.: 01865 271 606;
Fax: 01865 271 853; E-mail: grant.churchill@pharm.ox.ac.uk.
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