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NAADP induces pH changes in the lumen of acidic Ca2+ stores.

Abstract:
NAADP (nicotinic acid-adenine dinucleotide phosphate)-induced Ca2+ release has been proposed to occur selectively from acidic stores in several cell types, including sea urchin eggs. Using fluorescence measurements, we have investigated whether NAADP-induced Ca2+ release alters the pH(L) (luminal pH) within these acidic stores in egg homogenates and observed their prompt, concentration-dependent alkalinization by NAADP (but not beta-NAD+ or NADP). Like Ca2+ release, the pH(L) change was desensitized by low concentrations of NAADP suggesting it was secondary to NAADP receptor activation. Moreover, this was a direct effect of NAADP upon the acidic stores and not secondary to increases in cytosolic Ca2+ as it was not mimicked by IP3 (inositol 1,4,5-trisphosphate), cADPR (cyclic adenine diphosphoribose), ionomycin, thapsigargin or by direct addition of Ca2+, and was not blocked by EGTA. The results of the present study further support acidic stores as targets for NAADP and for the first time reveal an adjunct role for NAADP in regulating the pH(L) of intracellular organelles.
Publication status:
Published

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Publisher copy:
10.1042/bj20060759

Authors

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Institution:
University of Oxford
Division:
MSD
Department:
Pharmacology
Role:
Author


Journal:
Biochemical journal More from this journal
Volume:
402
Issue:
2
Pages:
301-310
Publication date:
2007-03-01
DOI:
EISSN:
1470-8728
ISSN:
0264-6021


Language:
English
Keywords:
Pubs id:
pubs:106519
UUID:
uuid:07875f46-351f-4806-90bc-5bb2d2c9f7a3
Local pid:
pubs:106519
Source identifiers:
106519
Deposit date:
2012-12-19
ARK identifier:

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