Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The functioning of ganules of blood platelets participating in the reversible endocytosis reaction was investigated in rabbits. Eczocytosis was shown to be initiated by inducers of two types: proteolytic enzymes and compounds accumulated by the granules (biogenic amines, dyes, anesthetics and phenothiazines). Heparin inhibits thrombin-induced eczocytosis. During eczocytosis produced by accumulation of compounds by blood platelet granules, the cells lose their capacity for maintaining the aggregation state. The nature of blood platelet granules participating in the reversible endocytosis reaction is discussed.
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PMID:[Reversible endocytosis apparatus of the blood platelets]. 46 19

In 12 dogs with acute experimental pancreatitis (AEP) and 6 control animals the "free", "latent" and "total" activity of acid phosphatase, beta-glucuronidase and cathepsins in whole homogenates of the pancreas, in a lysosomal-enriched subfraction and the supernatant of pancreatic tissue was estimated. AEP was induced by injection of bile salts and thrombin solution into the pancreatic duct. In 6 dogs the protection with heparin (1.5 mg/kg/body weight) immediately after producing AEP was applied. In AEP without any protection the free activity of hydrolases in the whole homogenate (80--90%) and in the lysosomal enriched subfraction (75--90%) was higher than in the controls (60--70% and 55--75% respectively), suggesting an augmented lysosomal fragility during the course of AEP. Heparin depressed the free activity of hydrolases to 60--80% in whole homogenates, and 64--75% in the lysosomal enriched subfraction. The release of cathepsins during incubation of the lysosomal-enriched subfraction in acidic medium was lower in the group with heparin treatment. The data obtained suggest the stabilising effect of heparin on the lysosomes of the pancreas during acute experimental pancreatitis in dogs.
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PMID:The effect of heparin on lysosomes of the dog pancreas during acute experimental pancreatitis. 47 25

Guinea pig antithrombin III has been purified from plasma by sequential heparin-Sepharose affinity chromatography, DE-52 cellulose chromatography, isoelectric focussing, and Sephadex G-100 gel filtration chromatography. The final product was homogeneous as judged by sodium dodecyl sulfate disc gel electrophoresis. Purification was 202-fold with a yield of 41%. Antiproteinase activity of antithrombin III was determined by progressive inactivation of thrombin coagulant and amidolytic activity. Heparin cofactor activity was demonstrated by immediate inactivation of thrombin by antithrombin III in the presence of minute quantities of heparin. It also could be demonstrated that thrombin inactivation by antithrombin III occurs by formation of a bimolecular complex whose rate of formation is markedly enhanced by minute quantities of heparin.
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PMID:Purification and properties of guinea pig antithrombin III. 50 72

Plasma heparin activity in 11 patients undergoing open-heart surgery was measured by comparing thrombin time of patient plasma to thrombin time of plasma containing known heparin concentrations. Although all patients received 300 units/kg of heparin, their initial plasma heparin levels varied significantly, from 1.8 units/ml in lighter petients to 3 units/ml in heavier patients. During hypothermia (25 degrees C), heparin decay was insignificant. At 37 degrees C, heparin decayed at a rate between 0.37 and 2.01 units/ml/hr. This decay was significantly faster in those patients with higher initial posthypothermia plasma heparin levels. When heparin was reversed with a protamine dose based on circulating plasma heparin levels, the mean difference between the predicted and the actual residual heparin activity was 0.025 units/ml. Heparin levels vary widely becuase of the influence of temperature on decay rates and because the space into which heparin is distributed is not simply proportional to weight. Evaluation and reversal of plasma heparin activity require ongoing analysis rather than any 1 dosage protocol.
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PMID:Plasma heparin activity and antagonism during cardiopulmonary bypass with hypothermia. 56 Jan 45

Studies were conducted to determine the effect of modifying specific functional groups of heparin on its antithrombin III-enhancing activity. The derivatives employed were heparin methyl ester, heparinylglycine and N-desulfated heparin. The carboxyl-modified derivatives increase the rate of inhibition of thrombin by antithrombin III, although not to the same extent as heparin. N-Desulfated heparin is devoid of any activity. Heparin methyl ester is more potent than heparinylglycine in activating antithrombin III, as exhibited by its immediate effect on the thrombin-fibrinogen reaction. However, heparinylglycine is the more effective of the two, in increasing the rate of thrombin deactivation by antithrombin III. The results indicate that although free carboxyl groups of heparin are not crucial for its binding to antithrombin III, they are important for the combination of the latter with thromobin. In contrast, N-sulfates are critical for the interaction of heparin with antithrombin III.
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PMID:Effect of heparin modification on its activity in enhancing the inhibition of thrombin by antithrombin III. 56 Feb 16

Inhibition of the esterase and amidase activities of bovine alpha- and beta-thrombin in the presence of antithrombin III and heparin has been studied. It was found that both the esterase and amidase activities of alpha-thrombin were inhibited by antithrombin III and the reactions were accelerated by heparin. The inhibition of amidase and esterase activities of beta-thrombin by antithrombin III has also been demonstrated. Heparin however did not increase the rate of inactivation of the enzyme.
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PMID:Inhibition of esterase and amidase activities of alpha- and beta-thrombin in the presence of antithrombin III and heparin. 57 Apr 23

The inhibitory capacity of antithrombin III (AT III) was measured by a quantitative method independent of the velocity of inhibition. When AT III was in excess of thrombin in plasma or in purified system the capacity of inhibitor decreased quantitatively in proportion to the amount of thrombin neutralized. Heparin present in reaction together with thrombin invariably induced a more extensive utilization of inhibitor than thrombin alone. The extent of this additional loss of inhibitory capacity was to a limited degree related to the concentration of heparin. Heparin itself was neutralized in thrombin-AT III reaction losing its anticoagulant property in proportion to the amount of thrombin bound by inhibitor. This quantitative neutralization of heparin occurred not only when the anticoagulant participated in thrombin-AT III binding but also when heparin was added to a medium containing a preformed thrombin-AT III complex. These results suggest that acceleration of binding and increased utilization of binding capacity are the two regular effects of heparin on thrombin-involving reactions of AT III. Both of these effects may be abolished by quantitative binding of heparin to thrombin-AT III complex.
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PMID:Antithrombin III and heparin inactivation in thrombin involving reactions. 57 90

A comparison has been made of some effects of a semi-synthetic heparin analogue, A73025, and heparin upon platelet function. In several of the in vitro tests performed, such as their potentiating effects on ADP and adrenaline induced aggregation and their effects on the aggregation of washed platelets by activated factor X, heparin proved to be more potent than A73025. Following intravenous injection of twice the quantity of A73025, an equivalent anti-factor Xa activity was obtained, in the agreement with our previous studies. However, it was found that PRP containing heparin and A73025 with comparable anti-Factor Xa acitvity responded differently to the addition of thrombin, as A73025 barely inhibited thrombin induced aggregation. Similarly, A73025 had little effect on the dilute thrombin clotting time of plasma, following intravenous injection. Heparin and A73025 were neutralized to approximately the same degree by a crude PF4 preparation.
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PMID:Comparison of heparin and a semi-synthetic heparin analogue, A73025. II. Some effects on platelet function. 60 58

The acute response of the hepatic circulation to thrombinaemia and endotoxinaemia were investigated in the anaesthetized dog. Small amounts of thrombin were infused into the hepatic artery and portal vein. The effects of thrombin were compared to those of minor amounts of portally infused endotoxin. Portal pressure increased significantly following portal infusion of thrombin and endotoxin. Both substances decreased the blood flow markedly in the hepatic artery, while that in the superior mesenteric artery and portal vein decreased only slightly. Heparin and polyphlorethin phosphate (PPP) abolished all effects of thrombin. Bradykinin infused simultaneously inhibited only the effect on the hepatic artery. Vasoactive intestinal peptide, which has the same vasodilatory effect in the liver, did not. It is believed that thrombin and perhaps endotoxin exert a vasoconstrictive effect mediated by products released from platelets.
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PMID:Effects of local thrombinaemia and endotoxinaemia on hepatic circulation in the anaesthetized dog. 61 32

Native rat mast cell macromolecular heparin proteoglycan and commercial hog heparin glycosaminoglycan chains inhibit generation of the amplification convertase, C3b, Bb. The inhibitory action of heparin is not due to chelation of magnesium. Heparin is most active in inhibiting convertase formation on cellular intermediates formed with the lowest C3b input and developed with the highest B concentration, thereby suggesting the receptor site for B on C3b as the point of heparin action. This interpretation is consistent with the demonstration that heparin prevents B utilization during the fluid phase interaction of C3b, B, and D. Inhibition is observed also when C3b,Bb generation takes place on cellular intermediates in the presence of P or C3NeF, which yield stabilized forms of the convertase. 50 times the concentration of heparin required to inhibit convertase generation does not accelerate the decay of the unstabilized or the C3NeF-stabilized convertases and has only a modest effect on the P-stabilized convertase. An additional effect of heparin is to impair beta1H-mediated decay-dissociation of C3b,Bb. The concentration of native or commercial heparin which prevents convertase formation is in the same range as that required for the demonstration of its anti-coagulant and anti-thrombin III cofactor activities. The additional finding that this inhibitory action of heparin can be expressed by the isolated mast cell granule suggests that native heparin may contribute to the modulation of the amplification pathway of complement.
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PMID:Modulation of the formation of the amplification convertase of complement, C3b, Bb, by native and commercial heparin. 62 4


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