期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 285, 期 48, 页码 37133-37137出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.C110.169763
关键词
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资金
- National Institutes of Health [HL90804, HL51314, HL086699]
- Biotechnology and Biological Sciences Research Council [BB/D012694/1, BB/G013721/1]
- BBSRC [BB/G008523/1, BB/D012694/1, BB/G013721/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/D012694/1, BB/G013721/1, BB/G008523/1] Funding Source: researchfish
Accumulating evidence implicates nicotinic acid adenine dinucleotide phosphate (NAADP) in the control of Ca2+-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 Ca2+ 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, Ca2+ 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 Ca2+ 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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