Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.5 (thrombin)
33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trans retinoic acid (t-RA) stimulated the production of tissue plasminogen activator (tPA) in HeLa-S3 and human umbilical vein endothelial cells (huvecs) in a dose-dependent manner with maximal release (four to five times control) at 40 nmol/L and 40 mumol/L, respectively. In endothelial cells, the stimulation of tPA production by phorbol 12-myristate 13-acetate (PMA) was potentiated 1.9-fold by 10 mumol/L t-RA, or 1.8 times the additive effect. In HeLa cells, total tPA secretion with 10 nmol/L PMA was increased from 43 ng/mL to 96 ng/mL by 40 nmol/L t-RA, which was two times the additive effect. Higher concentrations of t-RA (400 nmol/L) depressed tPA secretion by itself and also suppressed PMA-induced tPA production by 50%. Histamine and thrombin also synergized with t-RA. t-RA (40 nmol/L) and 10 micrograms/mL histamine or 10 U/mL thrombin combined to induce tPA production 3.4 and 1.3 times the additive effect in HeLa cells. Cyclic adenosine monophosphate (cAMP) levels were not significantly affected by 10 nmol/L to 10 mumol/L t-RA. Nor did 10 nmol/L PMA and 40 nmol/L t-RA together affect cAMP levels, suggesting that t-RA-mediated potentiation of PMA-induced tPA production occurred via a mechanism that was independent of cAMP levels. Downregulation of protein kinase C (PKC) by pretreatment of huvecs with 100 nmol/L PMA completely blocked a secondary response to PMA, but did not have a significant effect on t-RA induction. Pretreatment with 10 mumol/L t-RA, on the other hand, did not significantly affect a secondary stimulus by 100 nmol/L PMA, but completely suppressed a secondary stimulation by 10 mumol/L t-RA alone. These studies suggest that the mechanism mediating t-RA stimulation of tPA production interacts with the PKC pathway, resulting in synergism.
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PMID:Stimulation of tissue plasminogen activator production by retinoic acid: synergistic effect on protein kinase C-mediated activation. 132 47

Investigations were conducted to determine whether rabbit aortic smooth muscle cells (SMC) reproduce their essential in situ features in culture. Enzymatically isolated cells in culture were compared with their in situ state in terms of myosin and caldesmon isoform expression, sensitivity to Ca(2+)-mobilizing agonists, and contractility. Protein marker expression was assessed by electrophoresis and quantitative immunoblotting, and intracellular free Ca2+ ([Ca2+]i) measurements were accomplished using indo-1, a Ca(2+)-sensitive fluorescent dye. Contraction of SMC grown on deformable silicone films was monitored optically. Before the onset of cell division (3 to 6 days in culture), SMC still contained significant although decreasing amounts of smooth muscle myosin (SM1 and SM2 isoforms) and they started to express nonmuscle-type myosin. The relative content of 150-kDa caldesmon decreased, whereas the expression of 77-kDa caldesmon increased during this period. In the confluent primary culture (11 days), SM1 was expressed, but 150-kDa caldesmon was hardly detectable. Histamine (10(-5) mol/L), serotonin (10(-6) mol/L), and thrombin (1.5 units/mL) contracted deendothelialized rings of rabbit aorta, but only histamine was able to elevate [Ca2+]i 2.5- to 3-fold and induce reversible contraction of primary nondividing cells. [Ca2+]i elevation in response to histamine was due both to Ca2+ mobilization from intracellular stores and Ca2+ flux across the plasma membrane. After the onset of proliferation, SMC regained the ability to elevate [Ca2+]i in response to serotonin and thrombin but lost the ability to contract. Thus, primary cultured quiescent rabbit aortic SMC (3 to 6 days in culture) retain the essential features of vascular SMC in situ (eg, smooth muscle specific contractile and regulatory proteins, vasoactive hormone sensitivity, and contractility).
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PMID:Contractile rabbit aortic smooth muscle cells in culture. Preparation and characterization. 163 34

Human recombinant interleukin-3 (hrIL-3) released histamine from human leukocytes in vitro. The histamine release by hrIL-3 significantly correlated with those by anti-IgE, thrombin, and f-met. peptide, but not by A23187. Histamine release by hrIL-3 was a Ca2(+)-dependent reaction, as was that by anti-IgE, although the time course of histamine release by hrIL-3 was slower than that by anti-IgE. Pre-treatment of leukocytes with hrIL-3 decreased the histamine release by hrIL-3 itself, but enhanced the histamine releases by anti-IgE, f-met. peptide, thrombin and A23187. These results suggested that the mechanism of hrIL-3-induced histamine release was different from those of anti-IgE, f-met. peptide, thrombin, and A23187. There was no significant difference between hrIL-3-induced histamine release of leukocytes from asthmatics and healthy controls.
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PMID:[Histamine release from human leukocytes by human recombinant interleukin-3]. 169 56

Endogenous and exogenous free radical scavengers significantly decrease mast cell histamine release induced by coincubation with resting, activated platelets or with platelet-derived supernatant. Histamine and pyridylethylamine dose-dependently enhance platelet aggregation; the effect is potentiated by ranitidine and blocked by mepyramine. Histamine increases also cytosolic calcium concentration in platelets stimulated with thrombin, and binding sites for [3H]-mepyramine are present on platelet membranes.
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PMID:Definition of platelet-derived histamine-releasing factor and histaminergic receptors modulating platelet aggregation. 171 91

Histamine is known to be a mediator of inflammation. In order to understand the role of histamine in platelets, we have examined the effects of histamine on arachidonic acid (AA) release, cAMP accumulation, inositol trisphosphate production, and serotonin secretion. Incubation of rabbit (and human) platelets with histamine resulted in rapid increase of [3H]AA release from the platelets prelabeled with [3H]AA. The effect of histamine was blocked by the addition of H1 receptor antagonist mepyramine. Histamine did not substantially affect the cAMP content and inositol trisphosphate production. Histamine-stimulated AA release was not observed in digitonin-permeabilized platelets, whereas histamine acted synergistically with GTP or GTP analog, guanosine 5'-(3-O-thio)triphosphate. Histamine-stimulated, and GTP analog-dependent AA release was inhibited by guanosine 5'-(2-O-thio) diphosphate. The effects of three receptor stimulants, thrombin, norepinephrine, and histamine were both diminished by 1 microgram/ml of pertussis toxin treatment and by the antiserum against GTP-binding proteins (G proteins) treatment. However, the antiserum against beta gamma subunits of G proteins inhibited the histamine effect, not thrombin effect. 4 beta-Phorbol 12-myristate 13-acetate (PMA) treatment enhanced histamine-stimulated AA release and serotonin secretion but inhibited thrombin-stimulated reactions. The effect of PMA was dose dependent and was due to enhance the coupling of histamine receptors and G proteins. The results show the existence of H1 histamine receptors which couple phospholipase A2 activation via pertussis toxin-sensitive G proteins. Histamine actions differ in sensitivities to anti-beta gamma antiserum treatment and PMA treatment from thrombin actions.
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PMID:Histamine-stimulated and GTP-binding proteins-mediated phospholipase A2 activation in rabbit platelets. 215 20

A summarizing survey of different studies in atopic eczema involving three types of cells (platelets, neutrophils, basophils) and their mediators is given. Platelets were found to release normal amounts of serotonin upon stimulation with epinephrine, thrombin and slightly reduced amounts after aggregated IgG stimulation. Serotonin uptake by washed platelets was found to be slower in atopics than in normals. Neutrophils showed a decreased release of beta-glucuronidase to stimuli like zymosan or aggregated IgG in atopics compared to controls. This might be regarded as a contributory factor to the well-known decreased resistance to infections observed in atopic eczema. Basophils in most studies released increased amounts of histamine in the atopic population compared to controls, especially after stimulation with anti-IgE. Concomitantly to the histamine release there was a slight increase in prostaglandin E2 production both in atopics and normals, which was increased by preincubation with reduced glutathion-a coenzyme of PGE2 isomerase. Histamine release tended to occur faster in atopics. Two possible factors influencing releasability characteristics were studied, namely the cyclic nucleotide system and arachidonic acid (AA) dependent mechanisms. Leucocytes of atopics showed a decreased response of cAMP to beta-adrenergic and an increased response of cGMP to cholinergic stimulation. Significant augmentation of anti-IgE-induced histamine release was observed after cholinergic stimulation. AA metabolites obviously play a regulating role in mediator release. PGE2 inhibited histamine release to various stimuli both in atopics and in normals. Indomethacin enhanced histamine release, especially after anti-IgE stimulation in atopics, while it inhibited complement-dependent release reactions both in atopics and in normals. The exogenous inhibitors of lipoxygenase eicosatetraynoic acid (ETYA) and nordihydroguaretic acid (NDGA) inhibited histamine release equally in atopics and normals. The endogenous lipoxygenase inhibitor 15-HETE showed no inhibitory but rather a slight enhancing effect upon histamine release. It is concluded that patients with atopic eczema often exhibit altered releasability patterns to a variety of stimuli. On the basis of our findings we describe "altered releasability" as one factor of a vicious cycle between increased IgE-production, mediator secretion and T cell regulatory disturbances in the pathogenesis of atopic eczema.
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PMID:Altered releasability of vasoactive mediator secreting cells in atopic eczema. 240 33

Platelets, basophils and neutrophils from a patient with the Wiskott-Aldrich syndrome (WAS) were exposed to stimuli that activate specific membrane receptor or directly initiate biochemical events (e.g. the Ca2+ ionophore A23187 and ionomycin or arachidonic acid). Platelets from this patient did not aggregate in response to ADP, collagen, thrombin or adrenaline, which activate specific membrane receptors. Platelet aggregation, however, was normal in response to compound A23187, ionomycin or exogenous arachidonic acid. Histamine release from basophils of the WAS patient was normal in response to anti-IgE, a formylated peptide (f-met peptide), and to A23187. Similarly, the release of the lysosomal enzymes, beta-glucuronidase and lysozyme, from neutrophils of the WAS patient in response to serum treated zymosan (Zx), f-met peptide, and A23187 was not significantly different from that of his parents and 13 normal donors. These results suggest that the primary defect in WAS is selectively present in platelets and is located in a biochemical step between receptor activation and Ca2+ influx and/or initiation of arachidonate metabolism.
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PMID:The Wiskott-Aldrich syndrome: studies of platelets, basophils and polymorphonuclear leucocytes. 242 57

The ability of a variety of agonists to induce formation of inositol phosphates and 1,2-diacylglycerol in cultured adult human keratinocytes has been investigated. Histamine, bradykinin, and thrombin significantly stimulated formation of inositol mono-, bis-, and trisphosphate and 1,2-diacylglycerol within 5 min after addition. Aluminum fluoride also caused a dose-dependent accumulation of inositol phosphates suggesting the participation of a GTP binding protein in the regulation of phospholipase C-catalyzed phosphoinositide hydrolysis. These data demonstrate that human keratinocytes possess the capacity for phospholipase C-mediated signal transduction and suggest that this pathway may participate in the regulation of keratinocyte function.
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PMID:Agonist-induced hydrolysis of phosphoinositides and formation of 1,2-diacylglycerol in adult human keratinocytes. 247 31

Arachidonic acid metabolism was examined in endothelial cells cultured from bovine coronary arteries. In culture, these cells exhibit specific characteristics of endothelial cells. They form a contact-inhibited monolayer with a cobblestone appearance, contain immunoreactive von Willebrand's factor antigen, and have angiotensin I converting enzyme activity. Prostacyclin was the major prostaglandin synthesized from exogenous and endogenous arachidonic acid in these cells. In addition, exogenous arachidonic acid was metabolized to small amounts of prostaglandin E2 (PGE2) and several relatively nonpolar metabolites including 12-, 15-, and 11-hydroxyeicosatetraenoic acids (12-, 15-, and 11-HETE). Histamine, bradykinin, and thrombin increased PGI2 synthesis in these bovine coronary endothelial cells. Of these agonists, bradykinin was the most potent, increasing basal PGI2 release by fourfold. More vigorous stimulation of the cells with mechanical disruption of the cell monolayer, melittin, or A23187 resulted in release of both PGI2 and PGE2. Pretreatment of cells with exogenous arachidonic acid (10(-5) M) abolished their responsiveness to subsequent stimulation by arachidonic acid or vasoactive agents, but not PGH2. Furthermore, treatment of cells with 15-HPETE (10(-7)-10(-4) M), but not 15-HETE, specifically inhibited basal as well as A23187-stimulated PGI2 release. PGE2 release was increased slightly after 15-HPETE treatment. These studies indicate that bovine coronary endothelial cells can metabolize arachidonic acid to several biologically active products and that PGI2 synthesis by these cells is specifically related to the type of vasoactive agent employed. Both the qualitative pattern and quantity of eicosanoids synthesized by bovine coronary endothelial cells differ substantially from endothelial cells isolated from noncardiac vascular beds.
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PMID:Cultured bovine coronary arterial endothelial cells synthesize HETEs and prostacyclin. 312 93

Comparison of arachidonic acid metabolism by bovine coronary artery endothelial cells, bovine aortic endothelial cells and human umbilical endothelial cells indicated potentially important differences in relative amounts of the different prostaglandins produced. Bovine coronary endothelial cells converted 14C-arachidonic acid to radioactive 6-keto PGF1 alpha (the stable metabolite of PGI2) and to a lesser extent PGE2. Bovine aortic cells synthesized 6-keto PGF1 alpha and 6,15-diketo PGF1 alpha as the major products. PGE2, 6-keto PGE1, PGF2 alpha and PGD2 were minor metabolites. By comparison, endothelial cells isolated from human umbilical artery or vein formed mainly 6-keto PGF1 alpha and substantial amounts of PGF2 alpha, PGE2 and PGD2. Basal concentrations of 6-keto PGF1 alpha were two-fold higher in bovine coronary cells than in bovine aortic endothelial cells, but seven-fold less than in endothelial cells cultured from human umbilical vessels. Histamine, bradykinin and thrombin stimulated PGI2 synthesis in both coronary endothelial cells and human umbilical cells, but only bradykinin stimulated PGI2 synthesis in bovine aortic cells. This comparative study indicates that endothelial cells vary in the metabolites of arachidonic acid that they produce depending upon the vascular origin of the cells. Also, endothelial cells from different vascular beds respond differently to specific vasoactive agents.
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PMID:Prostaglandin synthesis in bovine coronary endothelial cells: comparison with other commonly studied endothelial cells. 312 91


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