Exogenous nitric oxide-induced release of calcium from intracellular IP3 receptor-sensitive stores via S-nitrosylation in respiratory burst-dependent neutrophils.

PMA-induced respiratory burst neutrophils were exposed to exogenous nitric oxide (NO) donor sodium nitroprusside (SNP) to study the effect of NO on calcium signaling. A sharp rise of cytosolic calcium concentration ([Ca(2+)](c)) was triggered by 1mM SNP with and without external calcium. We found that GF 109203X, a specific inhibitor of protein kinase C, DPI, a putative inhibitor of the respiratory burst-generating NADPH oxidase, and 2-DG, a non-metabolizable analog of glucose, completely inhibited the SNP-induced rise of [Ca(2+)](c) in PMA-activated respiratory burst neutrophils. Meanwhile, 2-APB and TMB-8, two potent IP(3) receptor inhibitors, prevented calcium increase respectively. Furthermore, N-ethylmaleimide (NEM), a specific cysteine alkylating agent, evidently abolished the [Ca(2+)](c) elevation. In contrast, the sGC inhibitor NS2028 had little effect on the rise of [Ca(2+)](c). Taken together, these results indicated that exogenous NO induced the release of calcium from intracellular IP(3) receptor-sensitive stores of neutrophils via S-nitrosylation in a respiratory burst-dependent manner.