Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A previous study revealed that elevation of platelet cyclic GMP induced by a pharmacological activator of soluble guanylate cyclase, 3-morpholinosydnonimine (SIN-1), induced a major inhibition of Ca2+ influx caused by thrombin, as detected by monitoring the fluorescence of the Ca2+ indicator quin-2. In contrast, activation of phospholipase C as well as Ca2+ mobilization presumably promoted by inositol-1,4,5-trisphosphate was less affected by SIN-1 treatment. In the present study, the effects of SIN-1 on Ca2+ influx have been investigated in more detail using platelets loaded with millimolar concentrations of quin-2. Under these conditions, Ca2+ entry from the medium into the platelet cytoplasm could be followed either by detecting fluorescence quenching by Mn2+ or by determination of 45Ca2+ uptake. Both events were inhibited by SIN-1 in a dose-dependent manner. Furthermore, the inhibition of 45Ca2+ uptake and of fluorescence increase observed in the presence of extracellular Ca2+ displayed remarkably parallel dose-response curves, suggesting that elevation of cyclic GMP brought about by SIN-1 inhibits the opening of "receptor-operated channels" whose precise nature remains to be determined.
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PMID:Inhibition of calcium influx in thrombin-stimulated platelets by SIN-1, an activator of soluble guanylate cyclase. 248 86

Ca2+ influx, Ca2+ mobilization and phospholipase C activation have been determined in human platelets stimulated by thrombin in the presence of increasing concentrations of SIN-1. Preliminary data indicate a major inhibitory effect of SIN-1 on Ca2+ influx, but also a significant inhibition of phospholipase C. However, the decrease of serotonin secretion by SIN-1 seems to be more related to phospholipase C inhibition. These data are discussed in relation to the known effects of SIN-1 on cGMP content of platelets.
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PMID:[Effects of SIN-1 on the activation of phospholipase C and calcium mobilization induced by thrombin in blood platelets]. 355 Jun 38

The mechanisms by which guanosine 3',5'-cyclic monophosphate (cGMP) modulates the contraction induced by ATP were investigated in small mesenteric resistance arteries of the rat. The nitric oxide donors 3-morpholinosydnonimine (SIN-1, 10 microM) and sodium nitroprusside (SNP, 10 microM) increased cGMP but not adenosine 3',5'-cyclic monophosphate (cAMP) content of the tissue. SIN-1, SNP, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP, 100 microM) inhibited the myosin light chain phosphorylation and the contractile response to ATP. Both effects were completely reversed by the selective inhibitor of cGMP protein kinase, Rp-8-bromoguanosine 3',5'-cyclic monophosphorothioate (30 microM). The sensitivity to Ca2+ of arteries permeabilized with Staphylococcus aureus alpha-toxin (4,000 hemolytic units/ml) was not affected by 8-BrcGMP. The two nitric oxide donors and 8-BrcGMP decreased the rise in intracellular Ca2+ induced by ATP. The vasodilator agents abolished the contractile response to the exogenous calcium in vessels that were exposed to 3 mM ATP after depletion of intracellular Ca2+ stores. Thapsigargin (1 microM), an inhibitor of the sarcoplasmic reticulum Ca(2+)-adenosinetriphosphatase, reversed the inhibitory effect of the vasodilator agents when the contraction induced by ATP was elicited in the presence of the Ca2+ entry blocker nitrendipine (1 microM) or in Ca(2+)-free medium. These results show that cGMP inhibits ATP-induced contraction by decreasing intracellular Ca2+ concentration in small resistance arteries. They indicate that this effect results from decreased Ca2+ influx and enhanced Ca2+ sequestration through a thapsigargin-sensitive pump via activation of a cGMP protein kinase.
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PMID:Effects of cGMP on calcium handling in ATP-stimulated rat resistance arteries. 790 Aug 76

Preceding the onset of insulin-dependent diabetes mellitus, pancreatic islets are infiltrated by macrophages secreting interleukin-1 beta, which exerts cytotoxic and inhibitory actions on islet beta-cell insulin secretion through induction of nitric oxide (NO) synthesis. The influence of the NO donor 3-morpholinosydnonimine (SIN-1) on insulin secretion from isolated pancreatic islets in response to various secretagogues was investigated. Stimulation of insulin release evoked by glucose, phospholipase C activation with carbachol, and protein kinase C activation with phorbol ester were obtained by SIN-1, whereas the response to adenylyl cyclase activation or K(+)-induced depolarization was not affected. It is concluded that enzymes involved in glucose catabolism, phospholipase C or protein kinase C, may be targeted by NO. Reversal of SIN-1 inhibition of glucose-stimulated insulin release by dithiothreitol suggests that NO may inhibit insulin secretion partly by S-nitrosylation of thiol residues in key proteins in the stimulus-secretion coupling. These adverse effects of NO on the beta-cell stimulus-secretion coupling may be of importance for the development of the impaired insulin secretion characterizing diabetes mellitus.
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PMID:Nitric oxide donor SIN-1 inhibits insulin release. 889 15

NIH-3T3 cells stably transfected with TrkB, the receptor for brain-derived neurotrophic factor (BDNF), were used to study the effects of NO and peroxynitrite on TrkB. 3-Morpholinosydnonimine (SIN-1), a donor of NO and O2- which immediately react to form peroxynitrite, induced TrkB tyrosine phosphorylation in a dose-dependent relationship from 2 to 40 mM. TrkB phosphorylation by SIN-1 was blocked by superoxide dismutase, which converts O2 to H2O2 and prevents its reaction with NO to form peroxynitrite, and by K252a, an inhibitor of TrkB phosphorylation by BDNF. Treatment with NO or O2- alone did not activate TrkB. Treatment directly with 1-4 mM peroxynitrite resulted in a dose-dependent increase in tyrosine phosphorylation of TrkB. SIN-1 treatment induced tyrosine phosphorylation of phospholipase C-gamma1 (PLC-gamma1) and induced its binding with activated TrkB, similar to that seen with BDNF downstream signaling pathways. These studies demonstrate activation of TrkB through peroxynitrite.
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PMID:Nitric oxide activation of TrkB through peroxynitrite. 1109 25

The effects of a range of nitric oxide (NO)-related compounds on histamine release from human basophils and rat peritoneal mast cells were studied. Basal and immunologic histamine releases from human basophils were not affected by N(omega)-nitro-L-arginine, N(omega)-nitro-L-arginine methyl ester, aminoguanidine or methylene blue (all inhibitors of NO production), sodium nitroprusside (an NO donor), L-arginine (a substrate for NO synthase) or D-arginine (the inactive enantiomer of L-arginine). In rat peritoneal mast cells, NO donors such as sodium nitroprusside, sodium nitrite and sodium nitrate, and lipopolysaccharide (an inducer of NO synthase) had little effect on basal histamine release, while 3-morpholino-sydnonimine (SIN-1, an NO donor), L-arginine and D-arginine increased this release by up to threefold. None of the inhibitors of NO production had any striking effect on histamine release induced by anti-rat immunoglobulin E (IgE), compound 48/80, sodium fluoride, phospholipase C, 1,2-dioctanoyl-sn-glycerol or ionophore A23187. However, haemoglobin was found to inhibit histamine release by anti-rat IgE or A23187 by ca. 40%. Alone of the NO donors, low concentrations of L-arginine produced a mild inhibition of histamine release induced by anti-IgE, compound 48/80 and A23187, but not other ligands, while sodium nitroprusside dose-dependently inhibited (by a maximum of ca. 30%) histamine release by anti-rat IgE, sodium fluoride or A23187. Stimulation with a variety of secretagogues or treatment with L-arginine, D-arginine, lipopolysaccharide, SIN-1 or sodium nitroprusside had no effect on NO production. Similarly, L-arginine, D-arginine or sodium nitroprusside did not change intracellular cGMP levels. On the basis of these results, it is suggested that NO does not play a significant role in the modulation of histamine release from human basophils or rat peritoneal mast cells. The effects of L-arginine, D-arginine and sodium nitroprusside may involve mechanisms unrelated to NO.
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PMID:Role of nitric oxide in histamine release from human basophils and rat peritoneal mast cells. 1151 42