SNAP is a nitric oxide (NO) donor, commonly used as a tool compound for studying the physiological and pharmacological roles of nitric oxide[1]. SNAP decomposes spontaneously or under the influence of light, heat, or metal ions to release nitric oxide, while generating the corresponding disulfide[2]. SNAP is widely employed to investigate the mechanisms of cardiovascular regulation, neurotransmission, and immune responses[3-4].
In vitro, treatment of Fu5 rat hepatoma cells with SNAP (1mM) for 8 hours significantly induced cytotoxicity[5]. Exposure of Lewis lung carcinoma cells (LLC-F6) and B16 melanoma cells (B16-4A5-F6) to SNAP (2mM) for 24 hours markedly reduced the viability of both cell types[6].
In vivo, a single intramuscular injection of SNAP (1.0mg/kg) administered 3 hours after the induction of critical limb ischemia (CLI) in SD rats significantly increased the ischemic-to-normal limb blood flow (INBF) ratio on day 14 and enhanced microvessel density in the ischemic area[7]. Continuous intracerebroventricular infusion of SNAP (0.1μM; 2μL) over 6 days in P2X7R+/+ and P2X7R−/− mice significantly elevated S-nitrosylation of protein disulfide isomerase (SNO-PDI) in the hippocampus and enhanced phosphorylation of NF-κB p65 at serine 276 in microglia[8].
References:
[1] Salas E, Moro MA, Askew S, et al. Comparative pharmacology of analogues of S-nitroso-N-acetyl-DL-penicillamine on human platelets. Br J Pharmacol. 1994 Aug;112(4):1071-6.
[2] Pravdic D, Vladic N, Cavar I, et al. Effect of nitric oxide donors S-nitroso-N-acetyl-DL-penicillamine, spermine NONOate and propylamine propylamine NONOate on intracellular pH in cardiomyocytes. Clin Exp Pharmacol Physiol. 2012 Sep;39(9):772-8.
[3] Mang CF, Kilbinger H. Modulation of acetylcholine release in the guinea-pig trachea by the nitric oxide donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP). Br J Pharmacol. 2000 Sep;131(1):94-8.
[4] Lu J, Katano T, Okuda-Ashitaka E, et al. Involvement of S-nitrosylation of actin in inhibition of neurotransmitter release by nitric oxide. Mol Pain. 2009 Sep 29;5:58.
[5] Ioannidis I, de Groot H. Cytotoxicity of nitric oxide in Fu5 rat hepatoma cells: evidence for co-operative action with hydrogen peroxide. Biochem J. 1993 Dec 1;296 ( Pt 2)(Pt 2):341-5.
[6] Hirano S. In vitro and in vivo cytotoxic effects of nitric oxide on metastatic cells. Cancer Lett. 1997 May 1;115(1):57-62.
[7] Yeh JN, Yip HK, Shao PL, et al. Combination of melatonin-delivered endothelial progenitor cells with S-nitroso-N-acetyl-DL-penicillamine for improving critical limb ischemia in the rat. Am J Transl Res. 2024 Sep 15;16(9):5020-5037.
[8] Kim JE, Wang SH, Lee DS, et al. Protein disulfide isomerase integrates toll-like receptor 4 and P2X7 receptor signaling pathways during lipopolysaccharide-induced neuroinflammation. Sci Rep. 2025 Mar 6;15(1):7906.