Document Detail

Acidic NAADP-sensitive calcium stores in the endothelium: agonist-specific recruitment and role in regulating blood pressure.
MedLine Citation:
PMID:  20876534     Owner:  NLM     Status:  MEDLINE    
Accumulating evidence implicates nicotinic acid adenine dinucleotide phosphate (NAADP) in the control of Ca(2+)-dependent functions. Little, however, is known concerning its role in the vascular endothelium, a major regulator of blood pressure. Here, we show that NAADP acetoxymethyl ester (NAADP-AM), a cell-permeant NAADP analog, increases cytosolic Ca(2+) concentration in aortic endothelial cells. We demonstrate that these signals and those evoked by acetylcholine are blocked by disrupting acidic organelles with bafilomycin A1. In contrast, Ca(2+) signals in response to thrombin are only partially inhibited by bafilomycin A1 treatment, and those to ATP were insensitive, suggesting that recruitment of acidic stores is agonist-specific. We further show that NAADP-evoked Ca(2+) signals hyperpolarize endothelial cells and generate NO. Additionally, we demonstrate that NAADP dilates aortic rings in an endothelium- and NO-dependent manner. Finally, we show that intravenous administration of NAADP-AM into anesthetized rats decreases mean arterial pressure. Our data extend the actions of NAADP to the endothelium both in vitro and in vivo, pointing to a previously unrecognized role for this messenger in controlling blood pressure.
G Cristina Brailoiu; Bogdan Gurzu; Xin Gao; Raman Parkesh; Parvinder K Aley; Diana I Trifa; Antony Galione; Nae J Dun; Muniswamy Madesh; Sandip Patel; Grant C Churchill; Eugen Brailoiu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-09-27
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2010-12-30     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  37133-7     Citation Subset:  IM    
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MeSH Terms
Blood Pressure / drug effects*
Calcium / metabolism*
Calcium Signaling / drug effects
Endothelium, Vascular / drug effects,  metabolism*
Macrolides / pharmacology
NADP / administration & dosage,  analogs & derivatives*,  pharmacology
Grant Support
BB/D012694/1//Biotechnology and Biological Sciences Research Council; BB/G013721/1//Biotechnology and Biological Sciences Research Council; HL086699/HL/NHLBI NIH HHS; HL51314/HL/NHLBI NIH HHS; HL90804/HL/NHLBI NIH HHS; R01 HL090804/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Macrolides; 0/nicotinic acid adenine dinucleotide phosphate acetoxymethyl ester; 53-59-8/NADP; 88899-55-2/bafilomycin A1; SY7Q814VUP/Calcium

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