CD38 mediates angiotensin II-induced intracellular Ca2+ release in rat pulmonary arterial smooth muscle cells

Suengwon Lee, Omkar Paudel, Yongliang Jiang, Xiao Ru Yang, James S.K. Sham

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


CD38 is a multifunctional enzyme that catalyzes the formation of the endogenous Camobilizing messengers cyclic ADP-ribose (cADPR) and nicotinic acid adenosine dinucleotide phosphate (NAADP) for the activation of ryanodine receptors (RyRs) of 2+ sarcoplasmic reticulum and NAADP-sensitive Ca release channels in endolysosomes, respectively. It plays important roles in systemic vascular functions, but there is little information on CD38 in pulmonary arterial smooth muscle cells (PASMCs). Earlier studies suggested a redox-sensing role of CD38 in hypoxic pulmonary vasoconstriction. This study sought to characterize its roles in angiotensin II (Ang II)-induced Ca2+ release (AICR) in PASMCs. Examination of CD38 expression in various rat arteries found high levels of CD38 mRNA and protein in pulmonary arteries. The Ang II-elicited Ca2+ response consisted of extracellular Ca2+ influx and intracellular Ca2+ release in PASMCs. AICR activated in the absence of extracellular Ca2+ was reduced by pharmacological or siRNA inhibition of CD38, by the cADPR antagonist 8-bromo-cADPR or ryanodine, and by the NAADP antagonist Ned-19 or disruption of endolysosomal Ca2+ stores with the vacuolar H+-ATPase inhibitor bafilomycin A1. Suppression of AICR by the inhibitions of cADPR- and NAADP-dependent pathways were nonadditive, indicating interdependence of RyR- and NAADP-gated Ca2+ release. Furthermore, ACR was inhibited by the protein kinase C inhibitor staurosporine, the nonspecific NADPH oxidase (NOX) inhibitors apocynin and diphenyleneiodonium, the NOX2-specific inhibitor gp91ds-tat, and the scavenger of reactive oxygen species (ROS) tempol. These results provide the first evidence that Ang II activates CD38-dependent Ca2+ release via the NOX2-ROS pathway in PASMCs.

Original languageEnglish (US)
Pages (from-to)332-341
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Issue number3
StatePublished - Mar 1 2015


  • Angiotensin II
  • CD38
  • Cyclic ADP-ribose
  • NADPH oxidase
  • Nicotinic acid adenosine dinucleotide phosphate

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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