CD38 Mediates Angiotensin II-induced Intracellular Ca(2+) Release in Rat Pulmonary Arterial Smooth Muscle Cells.

This study sought to characterize its roles in angiotension 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. 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. It was also reduced 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 non-additive indicating interdependence of RyR- and NAADP-gated Ca2+ release. Furthermore, AICR was inhibited by the protein kinase C inhibitor staurosporine, the non-specific NADPH oxidase (NOX) inhibitor 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. PMID: 25078456 [PubMed - as supplied by publisher]
Source: American Journal of Respiratory Cell and Molecular Biology - Category: Molecular Biology Authors: Tags: Am J Respir Cell Mol Biol Source Type: research