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

---

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

In 22 patients with acute myeloid leukaemia (17 cases of myeloblastic leukaemia, 4 cases of myelomonocytic leukaemia and 1 case of undifferentiated-cell leukaemia) platelets were isolated from the plasma by the method of Nicholls and Hampton as modified by Levy-Toledano by centrifugation in albumin gradient. The aim of platelet isolation was their "concentration" in cases of thrombocytopenia to values making possible aggregation tests, and platelet separation from the influence of plasma factors. Then aggregation of isolated platelets caused by ADP was studied. In 16 out of 22 patients a fall of aggregation was observed, with the mean values of aggregation rate and intensity were significantly lower. Parallelly done determinations of aggregating activity released from the platelets by thrombin showed lower values as compared with platelets from healthy subjects. In might be thought, in this connection, that the demonstrated reduction of isolated platelets is associated with a diminution of the nucleotide pool or disturbances of the platelet release reaction. The disturbances of the platelet release reaction. The disturbances of aggregation of isolated platelets and reduction of the aggregating activity were most pronounced in acute myelomonocytic leukaemia.
...
PMID:[Platelet function in acute myeloid leukemia. II. Aggregation of isolated platelets]. 28 Oct 86

A newly synthesized 13-aza derivative of prostanoic acid (13-APA) specifically inhibited human platelet aggregation induced by arachidonic acid, prostaglandin H2, or the stable endoperoxide analog (15S)-hydroxy-9 alpha,11 alpha-)epoxymethano)-prosta-5Z,13E-dienoic acid. 13-APA also inhibited [14C]serotonin release in response to arachidonic acid, ADP, or thrombin, but did not inhibit primary aggregation induced by ADP or thrombin. 13-APA completely blocked prostaglandin H2-induced aggregation in indomethacin-treated resuspended platelets but did not inhibit thromboxane synthesis. We therefore conclude that 13-APA acts as a direct antagonist of the platelet thromboxane/endoperoxide receptor.
...
PMID:13-Azaprostanoic acid: a specific antagonist of the human blood platelet thromboxane/endoperoxide receptor. 29 Oct 66

Platelet Factor VIII-related antigen (VIIIR:Ag) represents a significant proportion of the total circulating VIIIR:Ag pool. However, its participation in the events of primary hemostasis has not been shown. We now report that platelet-contained VIIIR:Ag is released from platelets by collagen, ADP and thrombin. The concentrations of these agonists, required for VIIIR:Ag release, are the same or lower than those required for release of serotonin, lysosomal enzymes, or fibrinogen. This release has the features of an energy-dependent secretory response because it is blocked by the metabolic inhibitors, antimycin A and 2-deoxy-D-glucose. The electrophoretic characteristics of the VIIIR:Ag released by collagen and ADP are similar to those of plasma VIIIR:Ag. However, thrombin-released platelet VIIIR:Ag differs from that of plasma in that the less anodal forms are relatively depleted. These differences do not appear to be the result of proteolytic degradation of platelet-derived VIIIR:Ag, but may reflect interactions between specific molecular forms of VIIIR:Ag and the platelet membrane. These studies suggest mechanisms by which platelet-contained VIIIR:Ag may contribute to the primary events of hemostasis.
...
PMID:Active release of human platelet factor VIII-related antigen by adenosine diphosphate, collagen, and thrombin. 31 83

We have shown previously that washed human platelets resuspended in Tyrode solution containing albumin and apyrase maintain their disc shape and their ability to aggregate upon the addition of low concentration of ADP, providing fibrinogen is added to the suspending medium. We have now examined their responses to other aggregating and release-inducing agents. Collagen, arachidonate, thrombin, immune serum globulin, the ionophore A23, 187 and phytohaemagglutinin from Phaseolus vulgaris caused aggregation and release of granule contents. The response to adrenaline was variable. Serotonin caused the platelets to change shape but no aggregation or release occurred. Addition of a small amount of plasma was necessary for ristocetin-induced aggregation. Polylysine caused immediate platelet-to-platelet adherence with little or no release of granule contents. Responses to collagen or thrombin were greater in a modified medium containing magnesium but no calcium; in this medium, aggregation caused by ADP or polylysine was followed by the release of granule contents whereas these agents caused aggregation without release in a medium with both calcium and magnesium. When protein was omitted from the suspending medium, platelet aggregation in response to ADP was variable. In this medium, collagen and thrombin caused more extensive release than in the albumin-containing medium. Aggregation by polylysine was accompanied by release and extensive lysis in the protein-free medium. Thus, the composition of the final resuspending medium has a major effect on the responses of washed human platelets to aggregating agents.
...
PMID:Properties of washed human platelets. 32 7

The mechanism of stimulus-response coupling in human platelets was investigated with a new instrument that simultaneously monitors aggregation and secretion in the same sample of plateletrich plasma. When platelets were stimulated by high concentrations of ADP, secretion began only after aggregation was almost complete. With lower concentrations of ADP or with epinephrine, biphasic aggregation was observed, and secretion began simultaneously with, or slightly after, the second phase of aggregation. When platelets were stimulated with high concentrations of gamma-thrombin or A23187, secretion and aggregation began essentially together. With very low concentrations of gamma-thrombin or A23187, biphasic aggregation was observed with secretion paralleling the second phase. At every concentration of collagen, secretion and aggregation appeared to be parallel events. Under every condition where the beginning of secretion lagged behind aggregation, secretion was dependent upon aggregation and was inhibited by indomethacin; this is referred to as aggregation-mediated platelet activation. When secretion began at the same time as aggregation, it also occurred in the absence of aggregation and was not blocked by indomethacin; this is referred to as directly induced platelet activation. These observations are consistent with a simple model of platelet stimulus-response coupling that includes two mechanisms for activation; aggregation-mediated activation is inhibited by indomethacin, while direct activation does not depend upon aggregation and is not inhibited by indomethacin. Secretion and second wave aggregation appear to be parallel events, with little evidence for second wave aggregation being a consequence of secretion as usually described.
...
PMID:Interrelations of platelet aggregation and secretion. 33 May 68

Prostacyclin (PGI(2)) is an unstable prostaglandin which inhibits platelet aggregation and serotonin release and causes vasodilation. The PGI(2) activity produced by monolayers of cultured human endothelial cells and fibroblasts was measured by the ability of their supernates to inhibit platelet aggregation in platelet-rich plasma, or to inhibit thrombin-induced [(14)C]serotonin release from aspirin-treated, washed platelet suspensions. Monolayers of cultured human endothelial cells, stimulated with sodium arachidonate, thrombin, the ionophore A 23187, or trypsin, secreted PGI(2) into the supernatant medium. Monolayers of fibroblasts produced PGI(2) activity only when stimulated by arachidonate. "Resting," intact monolayers did not produce detectable PGI(2), nor did monolayers treated with ADP or epinephrine. Production of PGI(2) activity was abolished by treatment of the monolayers with indomethacin, tranylcypromine, or 15-hydroperoxy arachidonic acid. The PGI(2) activity of the supernates was destroyed by boiling or acidification. Inhibition of thrombin with diisopropylfluoro-phosphate, and of trypsin with soybean trypsin inhibitor, abolished the stimulation of PGI(2) production by these enzymes. Production of thrombin at a site of vascular injury could, by stimulating PGI(2) synthesis by endothelial cells adjacent to the injured area, limit the number of platelets involved in the primary hemostatic response and help to localize thrombus formation.
...
PMID:Stimulation of endothelial cell prostacyclin production by thrombin, trypsin, and the ionophore A 23187. 36 56

We have evaluated the influence of NBT, vitamin E, and the combination of NBT and vitamin E on the fine structure and biochemistry of platelets during incubation, and the effects of these compounds on the aggregation and secretion of platelets stimulated by collagen, thrombin, epinephrine, and ADP. Results demonstrate that NBT and vitamin E, rather than injuring platelets, appear to protect them during incubation. Togheter NBT and vitamin E blockedaggregation by epinephrine, collagen, and thrombin, but permitted a small first wave stimulated by ADP. This pattern of response to aggregating agents was similar to reactions observed in platelets pretreated with aspirin and indomethacin, both potent inhibitors of platelet prostaglandin synthesis. The findings support the concept that conversion of arachidonic acid to an activated state is an important step in prostaglandin synthesis and that electron transfer or oxidation--reduction reactions are intimately involved in the development of platelet stickiness. Although vitamin E alone does not block prot to regulate formation of endoperoxides and thromboxanes.
...
PMID:Vitamin E and platelets: cooperative interactions with nitroblue tetrazolium on inhibition of adhesion, aggregation and secretion. 39 98

The individual and combined effects of PGD2, PGI2 and an aortic proteoglycan on human platelet aggregation and plasma clotting were studied. PGI2 was at least 10 times more potent than PGD2 in inhibiting platelet aggregation. Small doses of prostaglandins inhibited ADP- and thrombin-induced aggregation, but only prolonged aggregation time without affecting the extent of arachidonic acid (AA)-induced aggregation. Small doses of prostaglandins did not affect thrombin-induced clotting of PRP. Large doses of prostaglandins abolished platelet aggregation and prolonged the onset of thrombin-induced clotting. The aortic proteoglycan (APG) had no appreciable effect on ADP- or AA-induced aggregation. Small doses of APG abolished thrombin-induced clotting, while large doses of APG suppressed both clotting and aggregation induced by thrombin. PGI2 and PGD2 showed additive inhibition of platelet aggregation regardless how the aggregation was induced. APG and prostaglandins showed additive inhibition of only thrombin-induced aggregation. APG, but not any of the prostaglandins, prolonged clotting time of PPP. This prolongation was not potentiated by PGI2 or PGD2.
...
PMID:Combined effect of prostaglandins and an aortic proteoglycan on platelet aggregation and plasma clotting. 39 32

In rabbit platelets, the metabolically active ATP pool equilibrates with the releasable ATP pool within 1 day. The studies showing this have now been extended to human platelets. Human platelets labeled with 14C-adenosine or 14C-adenine were incubated for up to 10 hr in vitro at 37 degrees C. After 10 hr, about 12% of the total platelet 14C-ATP and 14C-ADP had become releasable with thrombin (4.2 units/ml). Lysis of platelets did not occur, since less than 1% of the platelet-bound 51Cr from platelets labeled with this radioisotope appeared in the ambient fluid upon thrombin treatment. The 14C-ATP/14C-ADP ratio of the released adenine nucleotides (7.6) was similar to the 14C-ATP/14C-ADP ratio of the nonreleasable adenine nucleotides (7.1) 2 hr after the labeling with 14C-adenosine. However, upon prolonged incubation (10 hr) in vitro, the 14C-ATP/14C-ADP ratio of the releasable adenine nucleotides decreased to 2.7. The adenylate energy charge and the 14C-ATP/14C-ADP ratio of the metabolic adenine nucleotide pool did not change significantly during the time of observation. The 14C-ATP content of the platelets decreased by less than 1% hr of incubation at 37 degrees C. These observations are interpreted to mean that the 14C is transferred from the metabolically active, nonreleasable adenine nucleotide pool of human platelets into the releasable adenine nucleotide pool as ATP and is partially hydrolyzed there to yield ADP. The transfer of ATP across the storage organelle membrane of platelets may be similar to transport processes in the chromaffin cells of the adrenal medulla and may represent a general phenomenon in cells that possess storage organelles containing adenine nucleotides.
...
PMID:Labeling of the releasable adenine nucleotides of washed human platelets. 40 62

Normal platelets incubated with anti-actin autoantibodies (AAA) (from the serum of patients with chronic aggressive hepatitis) do not show binding of these antibodies as seen by indirect immunofluorescence. AAA serum does not inhibit thrombin-induced clot retraction, despite the binding of the antibodies to platelets in the clot. Similarly, AAA serum does not affect "reversible" or "irreversible" aggregation (induced by ADP, collagen or epinephrine), despite the binding of the antibodies to platelet actin under such circumstances. AAA also bind to platelets when aggregation is inhibited by EDTA. The incubation of "reversibly" aggregated platelet with AAA results in a small but definite binding of AAA to platelets. These findings suggest that during "irreversible" and/or "reversible" aggregation, changes take place at the surface of platelets which expose the antigen at the surface of the cell.
...
PMID:Binding of anti-actin autoantibodies to platelets. 40 89


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---