S-Nitroso-N-acetyl-DL-penicillamine is a nitric oxide donor and a stable inhibitor of platelet aggregation[1][2][3][4].Under normoxic conditions at a concentration of 10 mM for 8 hours of action, S-Nitroso-N-acetyl-DL-penicillamine induces about 80% toxicity after 6 hours through the release of nitric oxide (NO)[1].In isolated rat ventricular myocytes, the half-life of S-Nitroso-N-acetyl-DL-penicillamine is approximately 6 hours. At a concentration of 100 μM for 30 minutes, S-Nitroso-N-acetyl-DL-penicillamine caused a sustained decrease in basal pHi in isolated rat ventricular myocytes[3].
SNAP 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human platelets
0.01-10 µM
10 min
Increase in intraplatelet cGMP concentrations
Br J Pharmacol. 1994 Aug;112(4):1071-6
Human platelets
3-10 µM
5 min
Inhibition of P-selectin release
Br J Pharmacol. 1994 Aug;112(4):1071-6
Human platelets
0.01-10 µM
1 min
Inhibition of collagen-induced platelet aggregation and ATP release
Br J Pharmacol. 1994 Aug;112(4):1071-6
Human platelets
3 or 10 µM
1-2 min
To study the inhibitory effect of SNAP on collagen-induced platelet aggregation, and found that ONOO- reversed the inhibitory effect of SNAP
Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6702-6
Dorsal root ganglia neurons
0.1-1 mM
1200 seconds
SNAP induced concentration-dependent increase in fluorescence intensity of DAF-treated neurons, and L-cysteine did not affect SNAP-induced fluorescence increase.
Neuropharmacology. 2013 Aug;71:1-9
Guinea-pig trachea strips with NK2 receptor antagonist SR 48968
100 µM
20 minutes
Examined SNAP's effect on acetylcholine release after NK2 receptor blockade. SNAP significantly inhibited release (78±3% of control).
Br J Pharmacol. 2000 Sep;131(1):94-8
Capsaicin-pretreated guinea-pig trachea strips
100 and 300 µM
20 minutes
Studied SNAP's effect on acetylcholine release after capsaicin pretreatment. SNAP's facilitatory effect was reversed to inhibition (74±4% and 78±2% of control), which was prevented by ODQ.
Br J Pharmacol. 2000 Sep;131(1):94-8
Epithelium-free preparation of guinea-pig trachea
100 and 300 µM
20 minutes
Investigated the effect of SNAP on electrically evoked [3H]-acetylcholine release. SNAP significantly increased release (121±4% and 124±10% of control), an effect abolished by the soluble guanylyl cyclase inhibitor ODQ (1 μM).
Br J Pharmacol. 2000 Sep;131(1):94-8
Rat colonic mucosal cells
0.1 – 1000 µM
20 minutes
To assess the extent of damage to colonic mucosal cells by SNAP, results showed increased cell damage as evaluated by Trypan blue dye uptake and lysosomal enzyme release.
Br J Pharmacol. 1999 Nov;128(6):1268-74
Arabidopsis nuclear extracts
10-1000 µM
20 minutes
To evaluate the effect of SNAP on HDAC activity; SNAP significantly inhibited nuclear HDAC activity (60% inhibition at 500 μM), reversible by DTT
Plant Physiol. 2017 Feb;173(2):1434-1452
BALB/cJ mouse peritoneal macrophages
500 µM
24 hours
SNAP inhibited the growth of MHV-3 in peritoneal macrophages from BALB/cJ mice.
J Virol. 1998 Sep;72(9):7084-90
A/J mouse peritoneal macrophages
500 µM
24 hours
SNAP inhibited the growth of MHV-3 in peritoneal macrophages from A/J mice.
J Virol. 1998 Sep;72(9):7084-90
RAW 264.7 cells
500 µM
24 hours
SNAP inhibited the growth of MHV-3 in RAW 264.7 cells, while NAP (an inactive analog of SNAP) had no effect.
J Virol. 1998 Sep;72(9):7084-90
NAc neurons
100 µM
30 minutes
Increased surface GluR2 expression by enhancing NSF S-nitrosylation and GluR2-NSF interactions
J Neurosci. 2014 Mar 5;34(10):3493-508
Human platelets
0.01-10 µM
5 min
Induction of disaggregation of ADP-aggregated platelets
Br J Pharmacol. 1994 Aug;112(4):1071-6
HEK293 cells
100 µM
5 minutes
To investigate the inhibitory effect of SNAP on N-type Ca2+ channel currents. Results showed that SNAP significantly inhibited N-type Ca2+ channel currents, and this effect was reversed by DTT.
J Biol Chem. 2015 Dec 18;290(51):30616-23
SHR rat coronary endothelial cells
100 µM
5 minutes
SNAP failed to modulate the α-thrombin-induced calcium transient.
Br J Pharmacol. 2000 Aug;130(7):1468-76
WKY rat coronary endothelial cells
10–100 µM
5 minutes
SNAP dose-dependently reduced the peak and decay time of α-thrombin-induced calcium transient. In one-third of the cells analyzed, 100 μM SNAP completely abolished the α-thrombin-induced calcium transient.
Br J Pharmacol. 2000 Aug;130(7):1468-76
SHR rat cardiomyocytes
1-200 µM
5 minutes
SNAP failed to further increase cGMP content
Br J Pharmacol. 2001 Oct;134(3):596-602
WKY rat cardiomyocytes
1-200 µM
5 minutes
SNAP dose-dependently increased cGMP content
Br J Pharmacol. 2001 Oct;134(3):596-602
Rat liver sinusoidal endothelial cells
2 mM
6 hours
To evaluate the cytotoxicity of low-concentration SNAP, results showed 15% cell death under hypoxic conditions.
Biochem J. 1996 Sep 15;318 ( Pt 3)(Pt 3):789-95
Rat liver sinusoidal endothelial cells
10 mM
6 hours
To assess the cytotoxicity of high-concentration SNAP, results showed 80% cell death under normoxic conditions.
Biochem J. 1996 Sep 15;318 ( Pt 3)(Pt 3):789-95
Human platelets
1 µM
60 min
Evaluation of stability of SNAP and SNFP, SNPL inhibitory activity decayed over time
Br J Pharmacol. 1994 Aug;112(4):1071-6
Arabidopsis protoplasts
500 µM
60 minutes
To assess SNAP's effect on HDAC activity in protoplasts; concentration-dependent inhibition (20% at 500 μM), blocked by cPTIO
Plant Physiol. 2017 Feb;173(2):1434-1452
Leishmania donovani amastigotes
10 to 160 μg/ml
72 hours
To assess the resistance of PMM-resistant strains to NO, showing enhanced resistance to NO at the intracellular amastigote stage.
Antimicrob Agents Chemother. 2019 Dec 20;64(1):e00904-19
Rat liver sinusoidal endothelial cells
5 mM
8 hours
To evaluate the cytotoxicity of SNAP under hypoxic conditions, results showed a significant increase in cell death to 90% under hypoxia compared to 45% under normoxia.
Biochem J. 1996 Sep 15;318 ( Pt 3)(Pt 3):789-95
SNAP 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Zucker rats
Obese Zucker rats (OZR) and lean Zucker rats (LZR)
In vitro (microvascular myographs)
0.3 nM
30 minutes
To assess the effect of ET-1 on endothelium-dependent and -independent relaxant responses in penile arteries, it was found that ET-1 inhibits NO-mediated endothelial relaxations via NADPH oxidase-dependent ROS generation and enhances vasoconstriction in obese animals.
Br J Pharmacol. 2014 Dec;171(24):5682-95
Sprague-Dawley rats
Cocaine behavioral sensitization model
Bilateral NAc injection
0.5 or 1 μg/side
Single injection, tested after 30 min
Dose-dependently attenuated the expression of cocaine-induced behavioral sensitization
J Neurosci. 2014 Mar 5;34(10):3493-508
BALB/c mice
CT26 colorectal cancer and 4T1 triple-negative breast cancer models
Intratumoral injection
1 μmol Hf (0.24 μmol SNAP)
4T1 model: 4 fractions of 2 Gy; CT26 model: 3 fractions of 3 Gy
SNAP/MOL(+) plus low-dose X-ray significantly inhibited tumor growth (TGI 81.2% in 4T1 model, 95.4% in CT26 model) and reduced lung metastasis
Adv Sci (Weinh). 2025 Feb;12(8):e2413518
Rats
Migraine model
Topical application
10 μM
30 minutes
To study the effect of SNAP on the mechanical sensitivity of meningeal nociceptors, results showed that SNAP promoted a delayed increase in mechanical sensitivity of nociceptors
Ann Neurol. 2013 Jun;73(6):741-50
Rats
Carrageenin-induced mechanical hyperalgesia
Local administration
200 µg/paw
Single dose, 30 minutes
SNAP inhibited carrageenin-induced mechanical hyperalgesia, and L-cysteine did not affect SNAP-induced anti-hyperalgesia.
Neuropharmacology. 2013 Aug;71:1-9
Rat
Isolated perfused heart model
Aortic cannula perfusion
5-10 nM
Single administration, lasting 30 sec
To investigate the protective effect of S-nitroso-N-acetyl-DL-penicillamine against peroxynitrite-induced vascular dysfunction. Results showed that SNAP at low concentrations did not induce vasodilatation but prevented the inhibition of vasodilator responses by peroxynitrite.
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12383-7
SNAP 动物研究
Animal study
At concentrations of 100 μM and 300 μM, S-Nitroso-N-acetyl-DL-penicillamine causes a small but significant increase in electrically evoked [3H]-acetylcholine release from guinea-pig trachea[4].
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