Disease relevance of Tocris-0756

• The mechanism of cytotoxicity of the NO donor 3-morpholino-sydnonimine toward a human ovarian cancer cell line (OVCAR) was examined [1].
• METHODS: Total plasma F2-isoprostanes were measured by gas chromatography-mass spectrometry (GC-MS) before and after the oxidation of plasma lipids with the peroxynitrite-generating compound, 3-morpholino-sydnonimine (SIN-1), in 23 patients with ESRD patients undergoing regular hemodialysis, and 14 controls [2].
• The NO generators sodium nitroprusside and 3-morpholino-sydnonimine were administered to induce NO toxicity in primary hippocampal neurons [3].
• Treatment with tetrodotoxin, Mg2+, or kynurenate did not affect the increase in BFcrb elicited by systemic hypercapnia or by topical application of the nitric oxide donor 3-morpholino sydnonimine (P > 0.05 from Ringer solution) [4].
• Because this effect was antagonized by 3-morpholino sydnonimine, nitric oxide production appears to contribute to the pathophysiology of amitriptyline-induced hypotension [5].

High impact information on Tocris-0756

• Recently, we found that the NO-donor SIN-1 (3-morpholino-sydnonimine) exerts a dual regulation of ICa in frog ventricular myocytes via an accumulation of cGMP [6].
• Several structurally unrelated nitric oxide donors, sodium nitroprusside, S-nitroso-N-acetylpenicillamine, 3-morpholino-sydnonimine, and acidified sodium nitrite, were effective [7].
• METHODS AND RESULTS: We examined the myocardial contractile effects of the NO-releasing nitrovasodilators sodium nitroprusside (SNP), 3-morpholino-sydnonimine (SIN-1), and S-nitroso-N-acetyl-penicillamine (SNAP); of a cGMP analogue, 8-bromo-cGMP; and of the cGMP-phosphodiesterase inhibitor zaprinast in isolated cat papillary muscle [8].
• The effects of the nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1) on the L-type Ca2+ current (ICa) were examined in frog ventricular myocytes under basal and phosphorylated conditions [9].
• Addition of the nitric oxide donors 3-morpholino-sydnonimine (SIN-1) or sodium nitroprusside significantly suppressed IL-1 beta-induced ICAM-1 molecule expression in a dose-dependent manner [10].

Chemical compound and disease context of Tocris-0756

• Two donor compounds, spermine NONOate, which can release authentic nitric oxide (NO), and 3-Morpholino-sydnonimine hydrochloride (SIN-1), which generates NO together with superoxide, possibly yielding peroxynitrite (ONOO-), were investigated in L5178Y mouse lymphoma cells for cytotoxic and genotoxic effects [11].

Biological context of Tocris-0756

• First we characterized the effect of peroxynitrite on the calcium homeostasis of HaCaT cells and demonstrated that both authentic peroxynitrite and the peroxynitrite generating compound 3-morpholino-sydnonimine triggered an elevation in intracellular calcium levels [12].
• In the presence of the NO donor, 3-morpholino-sydnonimine (SIN-1), pilocarpine no longer inhibited vagally induced bronchoconstriction [13].
• Different concentrations of the NO donors, S-nitroso-N-acetylpenicillamine (SNAP) or 3-morpholino-sydnonimine (SIN-1), did not alter this chemotaxis [14].
• Similarly, 3-morpholino-sydnonimine (SIN-1)-elicited formation of cyclic GMP in human cultured umbilical vein endothelial cells was inhibited by NS 2028 (IC50 30 nM) [15].
• Experiments were designed to examine whether 3-morpholino-sydnonimine (SIN-1) and iloprost have synergistic cardioprotective actions and whether their effects on infarct size are related to inhibition of platelet aggregation [16].

Anatomical context of Tocris-0756

• This study was designed to clarify the mechanism of the inhibitory action of a nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1) on human neutrophil degranulation [17].
• Oxygen modulation of guanylate cyclase-mediated retinal pericyte relaxations with 3-morpholino-sydnonimine and atrial natriuretic peptide [18].
• 1. The NO donor 3-morpholino-sydnonimine (SIN-1; 0.01-10 microM) evoked concentration-dependent relaxation of rat isolated mesenteric arteries pre-constricted with phenylephrine (1-3 microM) [19].
• Although Fos expression was increased with 3-morpholino-sydnonimine perfusion compared to that seen with artificial cerebrospinal fluid perfusion, there was still some Fos immunostaining in the control sections [20].
• We investigated the effect of propofol on endothelial cells subjected to the peroxynitrite (ONOO-) donor 3-morpholino sydnonimine (SIN-1) [21].

Associations of Tocris-0756 with other chemical compounds

• For this purpose, we studied the effects of NMDA and 3-morpholino sydnonimine (SIN-1) perfusions on the release of acetylcholine (ACh) in mouse striatum [22].
• However, after 10min of perfusion in the bath, 1microM and 10microM 3-morpholino-sydnonimine hydrochloride significantly modified the baseline of the mechanically evoked response, producing an increase in the mean spike discharge of the afferent fibers [23].
• 3. NO-induced inhibition of CCE was not mimicked by peroxynitrite (100 micro M), the peroxynitrite donor 3-morpholino-sydnonimine (SIN-1, 100 micro M) or 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP, 1 mM) [24].
• Intracerebroventricular (i.c.v.) injection of N omega-L-nitro-arginine methyl ester (L-NAME), 3-morpholino-sydnonimine (SIN-1), zinc deuteroporphyrin 2,4-bis glicol (ZnDPBG) or hemin did not change the basal vasopressin and oxytocin plasma levels [25].
• The effects of intracerebroventricular (i.c.v.) injections of L-arginine (L-Arg), a precursor of NO, N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase (NOS), and of sodium nitroprusside (SNP) and 3-morpholino-sydnonimine (SIN-1), NO donors, on basal prolactin levels were studied in conscious male rats [26].

Gene context of Tocris-0756

• This IL-1 beta-mediated induction of ICAM-1 and VCAM-1 expression was significantly inhibited in the presence of a NO donor 3-morpholino-sydnonimine (SIN-1) in a dose-dependent manner [27].
• Cells were pretreated with NO donors such as 3-morpholino-sydnonimine (SIN-1) or nitroprusside, and then stimulated with tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta (IL-1beta) [28].
• METHODS AND RESULTS: We examined the modulation of TGF-beta1 expression and activity and PKC activation in cultured rat heart myocytes exposed to a brief period of hypoxia-reoxygenation (H-R) by NO donor 3-morpholino-sydnonimine (SIN-1) [29].
• We describe the involvement of poly(ADP-ribose)polymerase 1 and 2 (PARP-1 and -2) and poly(ADP-ribose)glycohydrolase (PARG) in the response of rat germinal cells to the action of the NO donors, 3-morpholino-sydnonimine (SIN-1) and spermine nonoate (SNO) [30].
• In this study, we investigated the effects of the nitric oxide donor 3-morpholino-sydnonimine (SIN-1) on platelet and neutrophil adhesion, and the vasomotor response, in a porcine model of angioplasty [31].

Analytical, diagnostic and therapeutic context of Tocris-0756

• Animals received either SIN-1 (3-morpholino-sydnonimine; 10 micrograms/kg/min; n = 8) or placebo (n = 8) before and during angioplasty [32].
• Fos expression was also increased following the perfusion of 3-morpholino-sydnonimine, a nitric oxide donor, into the dorsal horn through a microdialysis fiber [20].
• By using the nitric oxide donor SIN-1 (3-morpholino-sydnonimine) the effects of direct intraarterial infusion of an exogenous source of nitric oxide in reperfused flaps was studied [33].
• PURPOSE: To investigate the development of intimal hyperplasia in response to percutaneous transluminal coronary angioplasty (PTCA) followed by local delivery of the nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1) [34].

References