| Acidic NAADP-sensitive calcium stores in the endothelium: agonist-specific recruitment and role in regulating blood pressure. | |
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MedLine Citation:
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PMID: 20876534 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-09-27 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-24 Completed Date: 2010-12-30 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 37133-7 Citation Subset: IM |
Affiliation:
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Departments of Pharmacology, University School of Medicine, Philadelphia, Pennsylvania 19140, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure / drug effects* Calcium / metabolism* Calcium Signaling / drug effects Endothelium, Vascular / drug effects, metabolism* Humans Macrolides / pharmacology NADP / administration & dosage, analogs & derivatives*, pharmacology Rats |
| Grant Support | |
ID/Acronym/Agency:
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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 HL090804-02/HL/NHLBI NIH HHS; R01 HL090804-03/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Macrolides; 0/nicotinic acid adenine dinucleotide phosphate acetoxymethyl ester; 53-59-8/NADP; 7440-70-2/Calcium; 88899-55-2/bafilomycin A1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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