Acidic NAADP-sensitive calcium stores in the endothelium: Agonist-specific recruitment and role in regulating 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

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)37133-37137
Number of pages5
JournalJournal of Biological Chemistry
Volume285
Issue number48
DOIs
StatePublished - Nov 26 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Acidic NAADP-sensitive calcium stores in the endothelium: Agonist-specific recruitment and role in regulating blood pressure'. Together they form a unique fingerprint.

  • Cite this

    Brailoiu, G. C., Gurzu, B., Gao, X., Parkesh, R., Aley, P. K., Trifa, D. I., Galione, A., Dun, N. J., Madesh, M., Patel, S., Churchill, G. C., & Brailoiu, E. (2010). Acidic NAADP-sensitive calcium stores in the endothelium: Agonist-specific recruitment and role in regulating blood pressure. Journal of Biological Chemistry, 285(48), 37133-37137. https://doi.org/10.1074/jbc.C110.169763