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At least 721 records · Page 40Linked to original sources
PubMed1988

Effect of fibrinopeptides A and B on human and rat platelet aggregation in vitro.

The effect of fibrinopeptides on platelet aggregation is reported. Fibrinopeptide A (minimal effective concentration, 0.65 microM) aggregated human (but not rat) platelets suspended in plasma and at lower concentrations (0.01-0.1 microM) potentiated platelet aggregation due to ADP and collagen in both species. Fibrinogen mimicked these effects of fibrinopeptide A. P-bromophenacyl bromide (100 microM), mepacrine (10 microM), indomethacin (10 microM) and dazoxiben (10 microM) inhibited human platelet aggregation induced by fibrinopeptide A and fibrinogen. In both species, fibrinopeptide B (0.65-6.5 microM) antagonised the platelet inhibitory effect of PGI2 and PGD2 but not adenosine. Antagonism was non-competitive in nature. The concentration of fibrinopeptide A required to potentiate platelet aggregation occurs naturally in the plasma of patients with thrombotic disease suggesting this effect may be of physiological significance during the formation of a thrombus. The novel action of fibrinopeptide B to reduce the platelet inhibitory effect of PGI2 and PGD2 may also contribute to the control of thrombus formation.

Adenosine Diphosphate↗
PubMed1976

Cyclic nucleotides and platelet aggregation. Effect of aggregating agents on the activity of cyclic nucleotide-metabolizing enzymes.

The activities of adenylate and guanylate cyclase and cyclic nucleotide 3':5'-phosphodiesterase were determined during the aggregation of human blood platelets with thrombin, ADP, arachidonic acid and epinephrine. The activity of guanylate cyclase is altered to a much larger degree than adenylate cyclase, while cyclic nucleotide phosphodiesterease activity remains unchanged. During the early phases of thrombin-and ADP-induced platelet aggregation a marked activation of the guanylate cyclase occurs whereas aggregation induced by arachidonic acid or epinephrine results in a rapid diminution of this activity. In all four cases, the adenylate cyclase activity is only slightly decreased when examined under identical conditions. Platelet aggregation induced by a wide variety of aggregating agents including collagen and platelet isoantibodies results in the "release" of only small amounts (1-3%) of guanylate cyclase and cyclic nucleotide phosphodiesterase and no adenylate cyclase. The guanylate cyclase and cyclic nucleotide phosphodiesterase activities are associated almost entirely with the soluble cytoplasmic fraction of the platelet, while the adenylate cyclase if found exclusively in a membrane bound form. ADP and epinephrine moderately inhibit guanylate and adenylate cyclase in subcellular preparations, while arachidonic and other unsaturated fatty acids moderately stimulate (2-4-fold) the former. It is concluded that (1) the activity of platelet guanylate cyclase during aggregation depends on the nature and mode of action of the inducing agent, (2) the activity of the membrnae adenylate cyclase during aggregation is independent of the aggregating agent and is associated with a reduction of activity and (3) cyclic nucleotide phosphodiesterase remains unchanged during the process of platelet aggregation and release. Furthermore, these observations suggest a role for unsaturated fatty acids in the control of intracellular cyclic GMP levels.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2004

Vinculin is proteolyzed by calpain during platelet aggregation: 95 kDa cleavage fragment associates with the platelet cytoskeleton.

The focal adhesion protein vinculin contributes to cell attachment and spreading through strengthening of mechanical interactions between cell cytoskeletal proteins and surface membrane glycoproteins. To investigate whether vinculin proteolysis plays a role in the influence vinculin exerts on the cytoskeleton, we studied the fate of vinculin in activated and aggregating platelets by Western blot analysis of the platelet lysate and the cytoskeletal fractions of differentially activated platelets. Vinculin was proteolyzed into at least three fragments (the major one being approximately 95 kDa) within 5 min of platelet activation with thrombin or calcium ionophore. The 95 kDa vinculin fragment shifted cellular compartments from the membrane skeletal fraction to the cortical cytoskeletal fraction of lysed platelets in a platelet aggregation-dependent manner. Vinculin cleavage was inhibited by calpeptin and E64d, indicating that the enzyme responsible for vinculin proteolysis is calpain. These calpain inhibitors also inhibited the translocation of full-length vinculin to the cytoskeleton. We conclude that cleavage of vinculin and association of vinculin cleavage fragment(s) with the platelet cytoskeleton is an activation response that may be important in the cytoskeletal remodeling of aggregating platelets.

Blood Platelets↗
PubMed1990

Bothrops jararaca snake venom: effects on platelet aggregation.

Crude venom from Bothrops jararaca has procoagulant, platelet aggregating and phospholipase A2 (PLA2) activities. By chromatographic fractionation of the venom on Sephacryl S-200 it was possible to separate these three activities and to show that distinct protein components are involved. The procoagulant activity appears to involve the synergistic action of several components and was not further studied in the present work. The aggregating activity results from the action of two components: 1) a serino-proteinase PMSF-inhibitable similar to thrombocytin and 2) a PMSF-resistant, calcium- and plasma-dependent factor distinct from other previously described aggregating principles. Fractions possessing PLA2 activity were also able to inhibit platelet aggregation induced by collagen and accelerated the slow reversal of aggregation induced by ADP. Both PLA2 activity and inhibition of collagen-induced platelet aggregation displayed by these fractions were abolished by reaction with p-bromophenacyl bromide and 2-mercapto-ethanol. These results indicate that in B. jararaca venom the PLA2 activity and the factor inhibiting platelet aggregation may be related to the same protein molecule.

Amides↗
PubMed2001

Effects of nebivolol on human platelet aggregation.

It has been documented that beta-adrenergic antagonists can influence platelet aggregation by a mechanism independent of their ability to antagonize beta-adrenoceptors. Nebivolol, a selective beta1-adrenergic receptor antagonist with additional hemodynamic effects, is able to vasodilate human forearm vasculature by acting on the L-arginine/nitric oxide pathway. Constitutive nitric oxide synthase is present also in human platelets, resulting in the formation of nitric oxide, an endogenous inhibitor of platelet aggregation. The aim of this study was to investigate the effects of nebivolol on platelet aggregation and in particular to determine the involvement of the platelet L-arginine/nitric oxide pathway. Propranolol, a nonselective beta-adrenergic antagonist, and carvedilol, a beta-blocker with vasodilating properties, were compared with nebivolol on platelet activity. Plasma from healthy male subjects was used. Platelet aggregation was achieved with adenosine diphosphate (ADP) (3 microM) and collagen (1 microg/ml), using the Born turbidimetric method to measure platelet aggregation. Our results showed that nebivolol, propranolol, and carvedilol all had an inhibitory effect on both ADP- and collagen-induced platelet aggregation. Nebivolol exhibited the greatest inhibition effect on platelet aggregation. The mechanism responsible for the inhibitory effect of nebivolol appeared to involve a nitric oxide-dependent pathway. Indeed, L-arginine augmented the inhibitory effects of nebivolol on platelet aggregation induced by collagen and ADP. Furthermore, the inhibitory effect of nebivolol on platelet aggregation was reduced in the presence of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). In conclusion, we have demonstrated in this study that nebivolol's mechanism of platelet aggregation inhibition differs from that of other beta-adrenergic antagonists by being partially dependent on nitric oxide production.

Adenosine Diphosphate↗
PubMed1989

Endothelin-1 releases prostacyclin and inhibits ex vivo platelet aggregation in the anesthetized rabbit.

The effects of porcine endothelin (endothelin-1, ET-1; 1 nmol/kg i.a.) on ex vivo platelet aggregation and platelet cAMP/cGMP levels were investigated in the anesthetized rabbit. ET-1 inhibited ADP-induced platelet aggregation by 83 +/- 9% within 5 min (p less than 0.01). This ET-1-induced inhibition of platelet aggregation lasted for 30 min and was associated with a significant (five- to sixfold) increase in platelet cAMP. However, platelet cGMP levels were unaffected. Indomethacin (5 mg/kg i.v., 20 min prior to ET-1) abolished the ET-1-induced inhibition of ex vivo platelet aggregation as well as the corresponding augmentation of platelet cAMP. Thus, ET-1 inhibits platelet function in vivo due to the release into the circulation of antiplatelet cyclo-oxygenase products, such as prostacyclin (or PGD2).

Anesthesia↗
PubMed1984

Inhibition of platelet aggregation and thromboxane synthesis after intake of small amount of icosapentaenoic acid.

Elderly people ingested 150 mg/day of icosapentaenoic acid (20:5n-3) or a placebo for one month. Platelet aggregation, platelet arachidonate metabolism and the fatty acid composition of both plasma and platelet lipids were investigated before and after the intake. Platelet aggregation induced by collagen, epinephrine or low concentrations of ADP was significantly reduced after 20:5n-3 intake. Besides, the main oxygenated product formation from endogenous platelet arachidonate under thrombin stimulation was markedly decreased after the 20:5n-3 supplementation. Such a decrease was absent after placebo. Moreover, no modification in the fatty acid composition of both plasma lipids and platelet phosphatidylcholine could be observed. We conclude that intake of low amounts of 20:5n-3 by elderly people, is able to lower their platelet sensitivity to aggregating agents, probably by decreasing the endogenous formation of platelet thromboxane A2, although no modification in the fatty acid composition was detected.

Adenosine Diphosphate↗
PubMed1992

Effect of taurine concentration on platelet aggregation in gestosis patients with edema, proteinuria and hypertension.

To elucidate the relationship between the high concentration of taurine in platelets and platelet aggregation in patients with EPH gestosis (gestosis with edema, proteinuria and hypertension), platelet aggregation and the platelet release response (release of ATP and beta-thromboglobulin) were studied in the washed platelet suspension (PS) obtained from normal pregnant or non-pregnant women and EPH gestosis patients. Platelet aggregation and platelet release response were significantly lower in EPH gestosis patients than in normal pregnant and non-pregnant women. Platelet aggregation, platelet release response induced by ADP and collagen and the aggregation induced by A23187 were inhibited in taurine-loaded PS from non-pregnant women. These results suggest that the decrease of platelet aggregation in EPH gestosis patients was caused by high concentrations of taurine in platelets, which may inhibit the intracellular Ca2+ movement and platelet release response. Therefore, taurine appears to have a protective effect against the hyper-coagulative state in EPH gestosis.

Adenosine Diphosphate↗
PubMed1992

Effects of low-dose aspirin and specific thromboxane synthetase inhibition on whole blood platelet aggregation and adenosine triphosphate secretion in healthy dogs.

Platelet aggregation and adenosine triphosphate (ATP) secretion in response to arachidonic acid (10 microM) or collagen (5 micrograms/ml) were compared in healthy, adult female Beagles treated with low-dosage aspirin (3.5 mg/kg of body weight, PO, q 12 h for 7 treatments) or with CGS 12970, a specific thromboxane synthetase inhibitor (10 mg/kg, PO, q 8 h for 10 treatments). Platelet aggregation was assessed in whole blood by use of an electrical impedance method. Baseline values obtained prior to treatment served as controls. Addition of arachidonic acid to blood from nontreated dogs resulted in significantly (P less than 0.001) increased impedance, but had no effect in blood from dogs treated with either aspirin or CGS 12970. Treatment with CGS 12970 or aspirin significantly (P less than 0.001) decreased platelet ATP secretion in response to arachidonic acid, compared with baseline values; however ATP secretion in aspirin-treated dogs was significantly (P less than 0.01) less than ATP secretion in CGS 12970-treated dogs. Differences in platelet aggregation were not observed between control dogs and aspirin- or CGS 12970-treated dogs in response to collagen as an aggregant, however, collagen-induced platelet ATP secretion was significantly (P less than 0.001) decreased in dogs treated with aspirin, compared with control values and values from dogs treated with CGS 12970. In dogs treated orally with 0.1, 0.2, 1.0, or 10 mg of CGS 12970/kg, dose-dependent inhibition of arachidonic acid-induced platelet aggregation was observed, with impedance changes not observed at the 10-mg/kg dosage and normal platelet aggregation associated with the 0.1-mg/kg dosage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed2002

Effects of immunosuppressive drugs on platelet aggregation in vitro.

Disturbances in platelet functions are found in kidney diseases and may contribute to the progression of atherosclerosis with its thrombotic complications. Kidney allograft recipients are particularly prone to dyslipidemia and have a high risk of cardiovascular death. The purpose of this work was to assess effects of various immunosuppressive drugs on aggregation of platelets obtained from healthy volunteers and chronically hemodialyzed patients. Platelet aggregation in the whole blood and in PRP was induced by collagen (2-microgram/ml whole blood and PRP) arachidonic acid (0.75 mM whole blood and PRP), ADP (10 microM--whole blood and 5 microM--PRP), ristocetin (0.75 mg/ml--whole blood and 1.5 mg/ml--PRP) and was studied after preincubation with clinically relevant concentrations of cyclosporine A, FK 506, 15-deoxyspergualin, azathioprine, mizoribine, mycophenolic acid and mycophenolate mofetil. Preincubation with cyclosporine A resulted in a significant increase in platelet aggregation, whereas preincubation with FK 506, azathioprine, mizoribine, mycophenolic acid and mycophenolate mofetil caused a decrease in platelet aggregation. 15-deoxyspergualin did not affect platelet aggregation. Enhanced platelet aggregation in CSA-treated kidney allograft recipients may have clinical implications in regard to the reported tendency to thrombosis in those patients, and to CSA-induced nephrotoxicity. Thus, inhibition of platelet activity in these patients might be of clinical benefit.

Humans↗
PubMed1997

A possible dual physiological role of extracellular ATP in the modulation of platelet aggregation.

ATP and ADP are simultaneously released from activated platelets in equimolar concentrations. Micromolar concentrations of ATP inhibit platelet aggregation by both competitive and non-competitive mechanisms. The current studies addressed the question of how platelets respond to agonists in the presence of nanomolar and micromolar concentrations of ATP and ADP alone or in combination. This is a significant issue since the concentration of ATP +/- ADP may vary widely within a microenvironment depending upon the source and cause for the release of the nucleotides. ATP (1-10 nM) was found to significantly enhance the thromboxane A2 analog, U44619-, collagen- and thrombin-induced platelet aggregations. Conversely, ATP at 1-100 microM inhibited these same reactions. ADP, in general, behaved exactly opposite to ATP. When equal amounts of ATP and ADP were added together the ADP response appeared to predominate. The observed ATP-induced response was not due to a hydrolytic product as evidenced by an unaltered response to ATP in the presence of adenosine deaminase or the ATP generating system, creatine phosphate plus creatine phosphokinase. Adenosine (1-10 nM), like ADP, inhibited agonist-induced platelet aggregation. The stimulation of agonist-induced platelet aggregation by 1-10 nM extracellular ATP appears to depend upon the phosphorylation of platelet membrane ecto proteins. The ATP analog, beta gamma-methylene ATP, that is incapable of serving as a phosphate donor for protein kinases, inhibited rather than stimulated agonist-induced platelet aggregation. The dual response of platelets to low and high concentrations of extracellular ATP +/- ADP may play a physiological role in hemostasis and thrombosis under normal and pathological conditions.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1987

[Studies on a platelet aggregation inhibitor isolated from the human placenta].

Platelet aggregation inhibitor (PPAI) from the human placenta was partially purified and the effects of PPAI on the platelet aggregation were investigated. The results are as follows. 1) The final recovery of PPAI was 1.7% of the starting microsomal fraction. 2) The molecular weight of PPAI was estimated to be 240,000 by gel filtration on a Sephadex G-200 column. 3) PPAI was completely inactivated by heating at 70 degrees C and trypsin digestion. 4) PPAI was found to inhibit the second phase of ADP or epinephrine induced aggregation. However, it did not affect the primary phase of aggregation. The inhibitor effect was also obtained when aggregation was induced by collagen and arachidonic acid (AA). 5) Platelet secretion was also inhibited by PPAI. 6) Malondialdehyde formation was significantly reduced by PPAI. 7) PPAI inhibited the platelet cyclooxygenase (PCO) pathway: Approximately 62% inhibition of the conversion of AA into thromboxane B2 (TXB2) was observed. These results indicate that PPAI may play an important role in the platelet aggregation inhibitor, in part, by suppressing the PCO pathway.

Blood Platelets↗
PubMed1984

[Studies on platelet aggregation induced by human cultured carcinoma cell lines].

Attempts were made to clarify the mechanism of platelet aggregation and to characterize the platelet aggregating material employing established human cancer cell lines. Eleven out of the nineteen human cancer cell lines investigated showed platelet aggregating activity. The existence of divalent cation was required for the platelet aggregation induced by HMV-1 tumor cells. The platelet aggregations induced by tumor cells (HMV-1, PC-10, 3LL) were not suppressed by specific thrombin inhibitor (MD-805). The platelet aggregating activities of tumor cells (HMV-1, M 7609) were diminished by treatment with trypsin but not with collagenase or neuraminidase. Aggregating activity was preserved with a preparation of membrane from these tumor cells, although it was abolished by heating(100 degrees C 15 min) or sonication. By SDS PAGE (autoradiography), membrane proteins with MW of 20,000 daltons which specifically bound to platelets were commonly found in cells with platelet aggregating activity (HMV-1, M 7609), but were absent in platelet non-aggregating cells (HGC-25). It is therefore concluded that platelet aggregation induced by human tumor cells does not require the coexistence of thrombin, but is evoked by direct interaction of platelets with aggregating proteins (MW 20,000 daltons) on the cell membrane.

Arginine↗
PubMed1994

Platelet aggregability in relation to the anaerobic threshold.

Platelet aggregability might be increased during physical exercise. This, in turn, has been explained by the elevation of plasma catecholamines and by the state of lactic acidosis, which occur at high exercise intensities. The purpose of this investigation was to study the relationship between changes in platelet aggregability and exercise intensity, the latter being determined in reference to the anaerobic threshold (AT). Each of sixteen male subjects performed an incremental exercise test in order to determine both (a) his running velocity (VAT) corresponding to his anaerobic threshold and (b) his running velocity (V4mM) corresponding to 95% of his running velocity eliciting a blood lactate concentration of 4 mM.l-1. Three and six days after this preliminary test, respectively, each subject performed an exercise test of 30 minutes, at a constant running velocity of either VAT or V4mM. Running velocity for each day's test was randomly assigned. Both capillary and venous blood samples were collected immediately before and immediately after each test, and after 30 minutes of recovery from each test, respectively. Capillary blood samples were obtained for determination of blood lactate concentration, whereas venous blood samples were obtained for determination of platelet count, and platelet aggregation in response to ADP and collagen, respectively. Platelet count significantly increased (p < 0.001) immediately after the 30-minute-tests at either VAT and V4mM, remaining elevated (p < 0.05) after 30 minutes of recovery from the tests at V4mM. The results did not evidence any significant increase in platelet aggregability with exercise, except for aggregation response to ADP immediately after the tests performed at V4mM (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Platelet aggregating activity mediated by thrombin generation in the NCG human neuroblastoma cell line.

Platelet aggregating activity of the NCG human neuroblastoma cell line was compared with that of the HL-60 human promyelocytic leukemia cell line. NCG, in intact cell suspensions and ultracentrifuged pellets, induced platelet aggregation most significantly in heparinized platelet rich plasma (PRP) containing 2.5 units/ml of heparin, but not in the presence of higher concentrations of heparin or 5 mM ethylenediamine-tetraacetate or in citrated PRP. NCG induced platelet aggregation was also inhibited by hirudin or (2R,4R)-4-methyl-1-[N2-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfon yl)-L- arginyl]-2-piperidinecarboxylic acid (MD 805) in the same manner as that of tissue thromboplastin induced platelet aggregation. HL-60 cells did not induce platelet aggregation in our heparinized PRP assay systems; however, after treatment with neuraminidase HL-60 cells became active in aggregating platelets in either heparinized or citrated PRP. NCG demonstrated high procoagulant activity by either intact cell suspensions or ultracentrifuged pellets. The procoagulant activity of NCG was reduced in Factor VII deficient human plasma as it was in the results obtained by tissue thromboplastin. These results suggest that NCG induces platelet aggregation via thrombin generated through procoagulant activity which is shed in association with microvesicles demonstrated in the ultracentrifuged pellets. This type of platelet aggregating activity found in NCG is significantly different from that of HL-60.

Adenosine Diphosphate↗
PubMed1984

Inhibition of platelet aggregation and endogenous lectin activity by oligoamines.

Amino sugars and basic amino acids inhibit platelet aggregation and the activity of the endogenous platelet lectin, yet, relatively high concentrations (approximately 30 mM) are required for the inhibition. If cooperative interactions are involved in these platelet surface activities, oligomers of primary amines should be more potent inhibitors than their individual component amines. Accordingly, series of oligomers of basic amino acids, of the polyamines (putrescine, spermidine and spermine) and of aliphatic diamines differing in chain length were tested for potency of inhibition of platelet aggregation and endogenous platelet lectin activity. Indeed, oligoamines were much more potent inhibitors of platelet aggregation than their corresponding monomers or shorter oligomers, more than accountable by an additive effect. For example, 60, 3 and 0.3 mM were needed for 50% inhibition of platelet aggregation by lysine, (lys)3 and (lys)5, respectively. A similar pattern was observed for the effect of the oligoamines on the activity of the endogenous platelet lectin. The inhibition of platelet aggregation by spermine is competitive, since the effect of a given dose of spermine decreased with increasing platelet concentration. Neither inhibition of platelet-inducer interaction nor Ca2+ insufficiency explain the inhibitory effects of the oligoamines. The results are consistent with the hypothesis that cooperative surface interactions underlie platelet aggregation and platelet lectin activity. The cooperative effects may reflect the formation of patches or clusters of positively charged groups on the surface of activated platelets.

Amino Acids↗
PubMed1993

Rapid and selective inhibition of platelet aggregation and thromboxane formation by intravenous low dose aspirin in man.

1. One of the major problems in the clinical use of low dose aspirin for the prevention of vascular occlusion is that it takes about 3-5 days to become effective, a time too long for patients with unstable angina or coronary thrombolysis. Intravenous aspirin may be expected to exert a more rapid effect, but its influence on endothelial prostacyclin synthesis is uncertain. 2. In a single-blind, randomized, prospective study, we compared the effects of a single intravenous low dose (50 mg) or high dose (500 mg) of aspirin or placebo infused over a 60 min period on platelet aggregation, platelet thromboxane A2 production and whole-body prostanoid synthesis in 10 healthy male subjects by gas chromatography-tandem mass spectrometry. 3. Before the study, blood flow rates in the basilic and subclavian veins were determined by sonographic colour velocity imaging; the infusion rate for low dose aspirin was calculated to avoid biologically effective plasma levels of aspirin in the systemic circulation. 4. Platelet aggregation induced by 1 mmol/l arachidonic acid was similarly inhibited by > 85% within 30 min after the start of the infusion of high dose or low dose aspirin, respectively, and remained suppressed for 24 h. Platelet thromboxane A2 release declined gradually after low dose aspirin, reaching a minimum of 93% inhibition after 60 min. High dose aspirin suppressed platelet thromboxane A2 release to below the detection limit after 10 min. 5. Urinary excretion of the major urinary metabolite of thromboxane A2 (2,3-dinor-thromboxane B2) was equally suppressed by both dosages of aspirin [no significant difference between high dose (-83.2%) and low dose (-67.4%)].(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

[The influence exercised by various temperatures on platelet aggregation in vitro].

To obtain a regular haemostasis is necessary that the platelets are numerically sufficient and functionally normal. Many factors influence on platelet aggregation; among these platelet shape, dimensions and volume. In our study we have analysed the temperature influence on platelet aggregation. In a group of 27 subjects we have demonstrated that the platelet rich plasma pre-incubation for 30 minutes in ice-bath does not modify the platelet aggregation capacity. On the contrary, the platelet rich plasma pre-incubation for 30 minutes at 37 degrees C reduces considerably the platelet aggregation, probably for the platelet volume reduction.

Adenosine Diphosphate↗