RESUMO
The presence of proteolytic enzymes such as cathepsin and elastase in platelets and the important role of collagen in platelet aggregation suggested that collagenase might be present in platelets. Epinephrine, ADP, and collagen liberate collagenase from platelets in plasma as measured by the hydrolysis of [(14)C]glycine-labeled collagen fibrils. The collagenase activity appeared in an early phase of platelet aggregation and was not a part of the release reaction. However, only 50% of the total collagenase could be liberated by the aggregating agents used. Sucrose density gradient analysis of platelet homogenates using appropriate sub-cellular markers indicated that collagenase appeared in both the granule and membrane fractions. Gel-filtered platelets failed to show collagenase activity before exposure to aggregating agents but released more collagenolytic activity than was found in platelet-rich plasma. This observation was explained by the finding that collagenolytic activity was inhibited by normal human plasma. One of the inhibitors is alpha(1)-antitrypsin as demonstrated by decreased inhibition in plasma from a patient with homozygous alpha(1)-antitrypsin deficiency. Platelet collagenase activity could also be demonstrated by its ability to decrease the viscosity of collagen solutions and to produce collagen fragments similar to those produced by other mammalian collagenases on disk gel electrophoresis. The observation that partially purified platelet collagenase could destroy the platelet-aggregating activity of collagen suggests that the enzyme might function in a negative feedback mechanism limiting thrombus formation.
Assuntos
Plaquetas/enzimologia , Colagenase Microbiana/sangue , Fosfatase Ácida/sangue , Difosfato de Adenosina/sangue , Animais , Aspirina/farmacologia , Plaquetas/metabolismo , Proteínas Sanguíneas/análise , Viscosidade Sanguínea , Soluções Tampão , Radioisótopos de Carbono , Cromatografia em Gel , Temperatura Baixa , Colágeno/metabolismo , Ácido Edético/farmacologia , Eletroforese Descontínua , Eletroforese em Gel de Poliacrilamida , Glucuronidase/metabolismo , Cobaias , Humanos , Colagenase Microbiana/antagonistas & inibidores , Colagenase Microbiana/isolamento & purificação , Colagenase Microbiana/metabolismo , Nucleotidases/sangue , Adesividade Plaquetária/efeitos dos fármacos , Serotonina/metabolismo , UltracentrifugaçãoRESUMO
The reaction between human platelet membrane glucosyl transferase and collagen has recently been proposed as the mechanism for pletelet-collagen adhesion. Collagen contains glucosyl-galactose and galactose side chains linked through the galactose to hydroxylysine. Oxidation of the 6-hydroxymethyl position of the galactosyl residue to aldehydes with galactose oxidase completely abolishes platelet aggregation. This enzymatic modification of collagen can be fully reversed by reduction of the aldehydes formed by NaBH(4) with complete restoration of platelet aggregating ability. Limited digestion with bacterial collagenase abolishes the ability of collagen to aggregate platelets. Removal of the N-terminal telopeptides from collagen with trypsin does not affect platelet aggregation. Tertiary structure of soluble collagen is essential for platelet aggregation. Normal collagen is less effective than lathyritic collagen, which contains only a small number of cross-links. The decreased number of aldehyde groups in the lathyritic collagen are not responsible for the increase in aggregating ability, since reduction with NaBH(4) does not alter platelet aggregation. These results suggest that integrity and accessibility of the galactose receptor site may be crucial for the formation of a ternary collagenenzyme-platelet membrane complex which must precede platelet aggregation.
Assuntos
Colágeno/farmacologia , Adesividade Plaquetária/efeitos dos fármacos , Oxirredutases do Álcool , Animais , Sítios de Ligação , Plaquetas/efeitos dos fármacos , Boroidretos , Bovinos , Eletroforese Descontínua , Galactose , Cobaias , Temperatura Alta , Humanos , Cinética , Latirismo , Colagenase Microbiana , Oxirredução , Ligação Proteica , Conformação Proteica , Desnaturação Proteica , Pele , Relação Estrutura-Atividade , TripsinaRESUMO
Eleven consecutive leukemia patients with thrombosis induced by asparaginase-prednisone-vincristine therapy were studied to gain insight into the pathogenesis of this complication. Measurement of anti-thrombin III, plasminogen, factor V, and fibrin degradation products as well as platelet aggregation sensitivity to adenosine diphosphate disclosed no consistent abnormalities that would explain pathologic thrombus formation. A decrease in platelet counts observed in nine of 11 patients, prompted us to investigate the possible involvement of factor VIII in this disorder. Levels of factor VIII procoagulant activity, von Willebrand factor (vWF) and ristocetin cofactor were similar to findings for an identically treated comparison group who remained free of thrombotic complications. However, qualitative examination of vWF by crossed immunoelectrophoresis (CIE) revealed a distinct right shift of the immunoprecipitin lines in each of three thrombotic patients tested, whereas a normal profile was found in three similarly treated patients without the complication. This altered pattern had reverted to normal when CIE was repeated 2 to 7 months later. We postulate that the abnormal vWF is related to the development of thrombosis.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fatores de Coagulação Sanguínea/análise , Leucemia Linfoide/tratamento farmacológico , Trombose/induzido quimicamente , Fator de von Willebrand/análise , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Asparaginase/administração & dosagem , Asparaginase/efeitos adversos , Testes de Coagulação Sanguínea , Criança , Pré-Escolar , Feminino , Humanos , Leucemia Linfoide/sangue , Masculino , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Trombose/sangue , Trombose/terapia , Fatores de Tempo , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
We examined a group of former oral contraceptive (OC) users, who had experienced cerebrovascular insufficiency, for the presence of hypercoagulable states. We found hypercoagulability in this group in the form of decreased plasma antithrombin III activity, increased platelet coagulant activity, and elevated plasma beta-thromboglobulin level. Certain characteristics (cigarette smoking, vascular headache, hyperlipidemia, and mitral valve prolapse) were encountered with increased frequency among former OC users who had experienced cerebrovascular insufficiency. The association of mitral valve prolapse with OC-related cerebrovascular insufficiency was particularly striking. We propose that preexisting hypercoagulable states, such as may exist in a subset of individuals with mitral valve prolapse, will magnify the risk of OC-related cerebrovascular morbidity.
Assuntos
Coagulação Sanguínea , Transtornos Cerebrovasculares/sangue , Anticoncepcionais Orais/efeitos adversos , Prolapso da Valva Mitral/complicações , Adulto , Antitrombina III/metabolismo , Transtornos Cerebrovasculares/induzido quimicamente , Transtornos Cerebrovasculares/complicações , Feminino , Humanos , Agregação Plaquetária , Contagem de Plaquetas , Estudos Retrospectivos , Risco , beta-Tromboglobulina/metabolismoRESUMO
Calcium (Ca) and magnesium (Mg) content were determined in muscle of 27 patients with Duchenne muscular dystrophy, 36 with other neuromuscular diseases, and 22 whose muscle biopsy specimens were histochemically normal. Muscle Ca was significantly elevated in all diseases studied but was about 50% higher in Duchenne dystrophy patients (p less than 0.0001). Mg was decreased by 44% in Duchenne dystrophy, compared with less striking deficits in other diseases (p less than 0.005). In older, nonambulatory Duchenne dystrophy patients, Mg was significantly lower than in younger, ambulatory patients (p less than 0.001); muscle Ca was the same in both groups. On the basis of noncollagen nitrogen concentration, muscle MG depletion could not be attributed solely to reduced muscle mass. These findings strengthen arguments for a role of Ca in the pathogenesis of muscular dystrophy and may implicate Mg depletion as another pathogenetic factor.
Assuntos
Cálcio/análise , Magnésio/análise , Músculos/análise , Distrofias Musculares/metabolismo , Adolescente , Criança , Pré-Escolar , Humanos , Doenças Neuromusculares/metabolismoRESUMO
The patient described had paroxysmal nocturnal hemoglobinuria associated with recurrent arterial as well as venous thrombosis. Study of platelet function revealed hypersensitivity to epinephrine, adenosine 5'phosphate (ADP) and collagen as judged by their ability to aggregate platelets as well as to release 14C serotonin. The release of total nucleotides was also markedly increased over normal with all aggregating agents. The abnormality was localized to the platelet since aggregation occurred when the patient's platelets were resuspended in normal plasma but not when normal platelets were incubated in the patient's plasma. Presumptive evidence for ongoing intravascular coagulation was an increase in fibrinogen derivatives of heavier molecular weight than the native protein presumably a result of thrombin action. However, factor XII was not activated and fibrinolysis was not increased. Complement component levels and antithrombin concentrations were also normal. The findings in this case suggest that hypersensitive platelets may contribute to the intravascular coagulation that is manifested by the increased incidence of thrombosis in patients with paroxysmal nocturnal hemoglobinuria.
Assuntos
Plaquetas/fisiologia , Coagulação Intravascular Disseminada/etiologia , Hemoglobinúria Paroxística/complicações , Tromboflebite/etiologia , Trombose/etiologia , Difosfato de Adenosina/farmacologia , Plaquetas/imunologia , Plaquetas/metabolismo , Colágeno/farmacologia , Proteínas do Sistema Complemento/metabolismo , Coagulação Intravascular Disseminada/imunologia , Epinefrina/farmacologia , Feminino , Hemoglobinúria Paroxística/imunologia , Humanos , Pessoa de Meia-Idade , Nucleotídeos/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Trombose/imunologia , Fatores de TempoRESUMO
BACKGROUND: Patients with peripheral arterial disease (PAD) have high rates of cardiovascular morbidity and mortality, including that caused by associated coronary heart disease and cerebrovascular disease. Previous studies have shown that coagulation parameters are altered in PAD and that altered coagulation may play a critical role in the susceptibility to cardiovascular complications in PAD. It is therefore important to assess the effect of secondary prevention measures on coagulation in patients with PAD. The Arterial Disease Multiple Intervention Trial (ADMIT), a multicenter, randomized, placebo-controlled trial, was conducted to determine the feasibility of a combined lipid-modifying, antioxidant, and antithrombotic treatment regimen in patients with PAD. The objective of this study was to assess the effect of the ADMIT interventions on coagulation. METHODS: ADMIT participants were randomly assigned to low-dose warfarin, niacin, and antioxidant vitamin cocktail or corresponding placebos in a 2 x 2 x 2 factorial design. Specialized coagulation studies were performed in a subset of 80 ADMIT participants at baseline and after 12 months of treatment. RESULTS: Low-dose warfarin (1 to 4 mg/d) resulted in a significant decrease in factor VIIc (P <.001) and in plasma F1.2 (P =.001). Unexpectedly, niacin treatment also resulted in significant decrease in both fibrinogen (48 mg/dL; P <.001) and F1.2 (P =.04). von Willebrand factor increased after antioxidant vitamin treatment (P =.04). CONCLUSIONS: A regimen of low-dose warfarin effectively modifies coagulation in patients with PAD. Niacin also favorably modifies fibrinogen and plasma F1.2. Niacin, in addition to its lipid effects, modifies abnormal coagulation factors that accompany PAD.
Assuntos
Anticoagulantes/uso terapêutico , Antioxidantes/uso terapêutico , Arteriopatias Oclusivas/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Niacina/uso terapêutico , Varfarina/uso terapêutico , Idoso , Arteriopatias Oclusivas/sangue , Ácido Ascórbico/uso terapêutico , Progressão da Doença , Quimioterapia Combinada , Estudos de Viabilidade , Feminino , Fibrinogênio/metabolismo , Humanos , Masculino , Vitamina E/uso terapêutico , beta Caroteno/uso terapêutico , Fator de von Willebrand/metabolismoRESUMO
Persistent gross hematuria associated with sickle hemoglobinopathy that fails to respond to conventional supportive therapy represents a difficult management dilemma. Two such patients with protracted, often painful, sickle trait macrohematuria are described. Both patients had normal renal anatomy and vasculature and had failed to respond to bed rest, intravenous hydration, and a trial of oral epsilon-aminocaproic acid. Patient 1 had normal coagulation function. Patient 2 had von Willebrand disease (decreased factor VIII antigen and quantitative ristocetin cofactor activity). Patient 1 responded to intravenous desmopressin acetate at a dose of 0.3 microgram/kg with a 155% increase in factor VIII clotting activity and a 135% increase in ristocetin cofactor and cessation of her macrohematuria within 18 hours after completion of the desmopressin infusion. She remained free of gross hematuria for 5 months with the exception of short-lived trauma-induced hematuria (in three voids) 6 weeks after desmopressin therapy. Patient 2 did not respond to intravenous desmopressin infusion despite a 234% and a 360% increase in factor VIII clotting activity and ristocetin cofactor, respectively. Intravenous desmopressin acetate may be helpful in halting protracted significant macrohematuria associated with sickle trait hemoglobinopathy in some patients when conventional management fails.
Assuntos
Anemia Falciforme/tratamento farmacológico , Desamino Arginina Vasopressina/uso terapêutico , Hematúria/tratamento farmacológico , Traço Falciforme/tratamento farmacológico , Doenças de von Willebrand/tratamento farmacológico , Adolescente , Fatores de Coagulação Sanguínea , Desamino Arginina Vasopressina/administração & dosagem , Feminino , Hematúria/etiologia , Humanos , Infusões Intravenosas , Masculino , Traço Falciforme/complicações , Traço Falciforme/fisiopatologia , Doenças de von Willebrand/complicações , Doenças de von Willebrand/fisiopatologiaRESUMO
11 patients with histories of clinical bleeding were selected as examples of platelet release abnormality. Mean bleeding time was 18 +/- 2.6 min (normal +/- SEM; 6 +/- 0.44); mean platelet adhesiveness was 9.9 +/- 4.3% (normal +/- SEM; 30 +/- 2.2). Clot retraction and platelet factor 3 were normal. Platelet aggregation with adenosine diphosphate (ADP), epinephrine and collagen was decreased, as was 14C-serotonin release. Electron microscopic studies of platelets exposed to epinephrine showed 2 subgroups: one which failed to aggregate or have centralization of organelles and a second which developed pseudopodia and centralization of organelles, but rarely aggregated or degranulated. Measurements of activity of adenylate cyclase and phosphodiesterase under basal conditions were performed on platelets from patients and control subjects. Adenylate cyclase activity was significantly lower and phosphodiesterase activity significantly higher in the patient group. Prostaglandin E1 was a potent stimulator of adenylate cyclase in both groups, as was NaF. It was concluded that the causative defects with "platelt release abnormality" do not reside in either the activity of adenylate cyclase or of phosphodiesterase. Changes in formation and destruction of cyclic adenosinemonophosphate (AMP) may instead be regarded as a compensatory response to a defect in another effector system.
Assuntos
Adenilil Ciclases/metabolismo , Transtornos Plaquetários/enzimologia , Diester Fosfórico Hidrolases/metabolismo , Adolescente , Adulto , Criança , Feminino , Humanos , MasculinoRESUMO
In a prospective study, we evaluated the effects of low-dose aspirin on maternal and neonatal plasma 6-keto-prostaglandin (PG) F1 alpha concentration, platelet aggregation, platelet thromboxane production, and neonatal transitional circulation. Forty women, at a mean (+/- SD) of 37 +/- 2 weeks' gestation, were randomized to receive (N = 10 each) placebo or 20, 60, or 80 mg of aspirin per day until delivery. Maternal serum 6-keto-PGF1 alpha levels were not affected by these doses of aspirin, whereas thromboxane B2 generated during clotting of maternal blood was decreased significantly by 60 and 80 mg of aspirin by 1 week of therapy. Maternal platelet thromboxane B2 production in response to adenosine diphosphate or collagen was reduced 98% by the 80-mg dose after 1 week of aspirin therapy. The 60-mg dose reduced maternal platelet thromboxane B2 production in response to adenosine diphosphate (50% decrease) or collagen (60% decrease) after 1 week of treatment, a nonsignificant difference. After 2 weeks of treatment with 60 mg of aspirin, platelet thromboxane B2 production induced by both collagen and adenosine diphosphate was inhibited significantly (P less than .01). Neonatal serum levels of 6-keto-PGF1 alpha and thromboxane B2 were not affected by any doses of aspirin. Further, neonatal platelet aggregation in response to platelet stimulation by collagen and adenosine diphosphate was not inhibited. All neonates had echocardiographic evidence of a patent ductus arteriosus, and noninvasive estimates of pulmonary arterial pressure were similar among the groups of infants.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Aspirina/farmacologia , Gravidez/sangue , Tromboxano B2/biossíntese , Alprostadil/metabolismo , Índice de Apgar , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Relação Dose-Resposta a Droga , Permeabilidade do Canal Arterial/tratamento farmacológico , Feminino , Humanos , Recém-Nascido , Troca Materno-Fetal , Agregação Plaquetária/efeitos dos fármacos , Terceiro Trimestre da Gravidez , Estudos ProspectivosRESUMO
The use of oral contraceptives (OC) has been associated with an increased risk of thromboembolic events in a subset of women. Factors predisposing to this problem are still not clearly defined although an increased platelet coagulant activity (CA) has been reported. This study was designed to evaluate the CA of platelets from asymptomatic current OC users compared with control subjects. The asymptomatic OC users were found to have evidence of hypercoagulability in the form of increased availability of platelet CA. These findings were present in both collagen stimulated and unstimulated platelets. In order to understand the mechanism we examined the in vitro effects of estradiol and/or progesterone on platelets. Platelets from normal males were incubated for one hour with estrogen and/or progesterone. There was no significant difference in CA of hormone treated platelets compared with control platelets from the same donor. CA was analyzed in platelets exposed to epinephrine, adenosine diphosphate, and collagen in the platelet aggregometer. Although a dose dependent effect was observed on CA of platelets exposed to the range of aggregating agents, the results show no significant difference between CA of the hormone treated and control platelets (p greater than 0.05). Likewise, platelet aggregation and release of nucleotide were not different between hormone treated and control platelets. Thus a direct effect of the hormones on platelets is an unlikely mechanism causing the increased CA seen in OC users.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Anticoncepcionais Orais/antagonistas & inibidores , Adulto , Plaquetas/metabolismo , Plaquetas/fisiologia , Epinefrina/farmacologia , Estradiol/farmacologia , Feminino , Humanos , Técnicas In Vitro , Masculino , Nucleotídeos/metabolismo , Concentração Osmolar , Agregação Plaquetária/efeitos dos fármacos , Progesterona/farmacologia , Valores de Referência , Esteroides/efeitos adversosRESUMO
The contribution of platelet factor V to prothrombin conversion was studied in a purified two-stage system designed to measure the ability of factor V to accelerate prothrombin conversion. When unstimulated gel-filtered platelets (GFP) were substituted for both factor V and phospholipid, thrombin evolution was linear following a long lag time. Gel filtration resulted in considerable phospholipid availability with minimal factor V release. Incubating platelets with collagen in increasing concentrations resulted in marked shortening of the lag time, an increase in the initial rate of thrombin formation, and release of platelet factor V. The inhibition of thrombin formation by preincubation of the platelets with metabolic inhibitors is consistent with previous observations that factor V is released from alpha-granules by collagen in a process requiring metabolic energy. Released platelet factor V added to metabolically inhibited platelets reproduces the acceleration of prothrombin conversion demonstrated in GFP incubated with collagen. Furthermore no acceleration of the clotting time at collagen concentrations used in this study was demonstrated in an assay designed to measure available platelet phospholipid in the presence of excess factor V. The rate of increased thrombin generation produced by collagen stimulation is primarily due to released platelet factor V in the system employed.
Assuntos
Fatores de Coagulação Sanguínea/fisiologia , Plaquetas/fisiologia , Protrombina/metabolismo , Trombina/biossíntese , Animais , Coagulação Sanguínea , Bovinos , Colágeno/farmacologia , HumanosAssuntos
Colágeno/metabolismo , Adesividade Plaquetária , Agregação Plaquetária , Polímeros/biossíntese , Animais , Anuros , Metabolismo dos Carboidratos , Carboidratos/análise , Clostridium/enzimologia , Colágeno/análise , Colagenase Microbiana , Oxirredução , Ácido Periódico/metabolismo , Agregação Plaquetária/efeitos dos fármacos , TemperaturaAssuntos
Colágeno/análise , Conformação Molecular , Adesividade Plaquetária , Agregação Plaquetária , Polímeros/biossíntese , Animais , Arginina/efeitos adversos , Colágeno/antagonistas & inibidores , Colágeno/fisiologia , Cobaias , Hemostasia , Humanos , Penicilamina/efeitos adversos , Iniciação Traducional da Cadeia Peptídica , Plasma/análise , Agregação Plaquetária/efeitos dos fármacos , Polímeros/análise , Temperatura , Fatores de TempoAssuntos
Transtornos Cerebrovasculares/prevenção & controle , Inibidores da Agregação Plaquetária/administração & dosagem , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Ensaios Clínicos como Assunto , Humanos , Ataque Isquêmico Transitório/prevenção & controle , Inibidores da Agregação Plaquetária/efeitos adversos , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Resultado do TratamentoRESUMO
Human platelets are less responsive to PAF at 37 degrees than at 25 degrees. They can be desensitized to the effects of PAF by pre-exposure to small concentrations. In both cases desensitization appears to be accompanied by a decreased affinity of the high affinity site for PAF rather than loss of binding sites. Alteration of a metabolic step subsequent to binding cannot be excluded, but platelets show normal response to a variety of other agents under the conditions resulting in desensitization of platelets to PAF.
Assuntos
Plaquetas/efeitos dos fármacos , Fator de Ativação de Plaquetas/farmacologia , Difosfato de Adenosina/farmacologia , Colágeno/farmacologia , Relação Dose-Resposta a Droga , Epinefrina/farmacologia , Humanos , Cinética , Agregação Plaquetária/efeitos dos fármacos , Temperatura , Trombina/farmacologiaRESUMO
PAF causes dose dependent platelet aggregation of human platelet rich plasma or gel filtered platelets (GFP). The benzodiazepines alprazolam and triazolam, but not diazepam (1-10 microM), inhibit PAF induced aggregation but have no effect on aggregation induced by other platelet agonists such as ADP, epinephrine and collagen. The IC50 for aggregation by PAF (4 nM) in GFP is 1 microM for both alprazolam and triazolam. The mechanism for this inhibition was explored by studying the binding of 3H-PAF(0.08 nM) to GFP in Tyrodes buffer containing albumin (0.35%), Mg++ (1mM) and Ca++ (0.5mM). GFP was incubated with different doses of the drug for 5 min prior to addition of 3H-PAF. Incubation was then carried out for 60 min at 25 degrees C to achieve binding equilibrium, as previously established. Alprazolam and triazolam, but not diazepam, caused competitive displacement of 3H-PAF from specific binding sites of GFP. The IC50 of alprazolam was 3.8 microM while that of triazolam was 0.82 microM. Lineweaver-Burk plots of 3H-PAF binding in the presence of inhibitor were also consistent with competitive inhibition. These results are consistent with the interpretation that the specific inhibition of PAF induced platelet aggregation by alprazolam and triazolam, respectively, is due to competitive inhibition of binding of PAF to its receptor.
Assuntos
Alprazolam/farmacologia , Plaquetas/efeitos dos fármacos , Fator de Ativação de Plaquetas/metabolismo , Triazolam/farmacologia , Alprazolam/metabolismo , Ligação Competitiva , Plaquetas/metabolismo , Diazepam/metabolismo , Diazepam/farmacologia , Humanos , Técnicas In Vitro , Cinética , Agregação Plaquetária/efeitos dos fármacos , Triazolam/metabolismoRESUMO
Factor V, a plasma protein cofactor necessary for optimal conversion of prothrombin to thrombin, is also present in considerable concentration in blood platelets (9.9 units per 10(9) platelets). Subcellular fractionation by two methods has localized factor V in the alpha granules of unstimulated platelets. ADP and epinephrine cause release of 4.6% and 6.4%, respectively, of the total factor V, a process completely inhibited by cyclooxygenase alkylation by aspirin. In contrast, collagen causes release of 25% of platelet factor V, a process only partially suppressed by aspirin. Secretion of factor V depends on the availability of metabolic energy, because antimycin A, an inhibitor of aerobic metabolism, and 2-deoxyglucose, an inhibitor of anaerobic glycolysis, together almost totally inhibited the secretion of factor V induced by collagen. The data establish that factor V is not normally available on unstimulated platelets but can be secreted from alpha granules upon stimulation with physiological agents such as ADP, epinephrine, and collagen. Because factor V is known to serve as a receptor for factor Xa, the exposure of factor V on platelets consequent to release would accelerate the process of blood coagulation.
Assuntos
Plaquetas/metabolismo , Fator V/metabolismo , Difosfato de Adenosina/farmacologia , Aspirina/farmacologia , Transporte Biológico Ativo/efeitos dos fármacos , Compartimento Celular , Colágeno/farmacologia , Epinefrina/farmacologia , Humanos , Polietilenoglicóis/farmacologia , Prostaglandinas/biossíntese , Serotonina/metabolismoRESUMO
Prostaglandin I2 (PGI2) is hydrolyzed more slowly in human plasma than in buffer at the same pH; this stabilization appears to be due to binding of PGI2 to albumin. The stability of the antiaggregatory potency of PGI2 is similar in human blood and in plasma buffered to pH 7.55. No measurable conversion of [3H]-PGI2 to radioactive or nonradioactive metabolites occurred during incubation with blood.