scholarly journals THE TUMOR-PROMOTER PHORBOL ESTER (12-0-TETRADECANOYL-PHORBOL-13-ACETATE), A POTENT AGGREGATING AGENT FOR BLOOD PLATELETS

1974 ◽  
Vol 60 (2) ◽  
pp. 325-336 ◽  
Author(s):  
Marjorie B. Zucker ◽  
Walter Troll ◽  
Sidney Belman
Keyword(s):  
Platelet Aggregation ◽  
Cyclic Amp ◽  
Phorbol Ester ◽  
Platelet Rich Plasma ◽  
Direct Action ◽  
Blood Platelets ◽  
Tumor Promoter ◽  
Metabolic Inhibitors ◽  
Rapid Phase ◽  
Low Concentrations

The phorbol ester 12-0-tetradecanoyl-phorbol-13-acetate, a potent tumor-promoting agent, caused irreversible platelet aggregation when more than 0.02 µM was stirred with human citrated or heparinized platelet-rich plasma (PRP). With washed platelets, 1 nM was effective. The alcohol phorbol, which has little tumor-promoting activity, failed to cause platelet aggregation. With all but low concentrations of phorbol ester, aggregation was succeeded by a rapid phase. The latter was prevented or reduced by enzymes which destroy ADP and by aspirin, was associated with a change in platelet shape, and was presumably due to released ADP. At higher concentrations, only a rapid phase was seen, and these inhibitors were not effective. Low concentrations did not aggregate platelets in PRP containing sufficient EDTA or EGTA to chelate ionized calcium or in PRP from thrombasthenic patients; higher concentrations caused slight aggregation. Both the primary, non-ADP-dependent aggregation and the rapid ADP-dependent aggregation were markedly inhibited by substances which increase cyclic AMP, metabolic inhibitors, and the sulfhydryl inhibitor N-ethylmaleimide. Phorbol ester reduced platelet cyclic AMP only when it had been previously elevated by prostaglandin E1. 1 µM did not release ß-glucuronidase, lactic dehydrogenase, or inflammatory material from platelets in 4–5 min despite marked aggregation, but liberated all three in 30 min. The possibility is discussed that low phorbol ester concentrations cause primary aggregation by a direct action on platelet actomyosin.

The Effect of Mitomycin C on Platelet Aggregation and Adenosine 3′, 5′-Monophosphate Metabolism

1978 ◽  
Vol 39 (01) ◽  
pp. 177-185 ◽  
Author(s):  
Shuichi Hashimoto ◽  
Sachiko Shibata ◽  
Bonro Kobayashi
Keyword(s):  
Platelet Aggregation ◽  
Cyclic Amp ◽  
Mitomycin C ◽  
Blood Platelets ◽  
Adenosine Diphosphate ◽  
Cellular Membrane ◽  
Adenyl Cyclase ◽  
Cyclic Amp Phosphodiesterase ◽  
Membrane Structure And Function ◽  
And Function

SummaryThe effect of Mitomycin C on aggregation, adenosine 3′, 5′-monophosphate (cyclic AMP) metabolism and reactions induced by thrombin was studied in rabbit platelets. Mitomycin C inhibited the platelet aggregation induced by adenosine diphosphate or thrombin. The level of radioactive cyclic AMP derived from 8-14C adenine or 8-14C adenosine increased after incubating intact platelets with Mitomycin G. Formation of radioactive adenosine triphosphate also increased though mitochondrial oxidation was not stimulated. Similar effect was observed also in rabbit liver. Mitomycin C failed to stimulate platelet adenyl cyclase but inhibited cyclic AMP phosphodiesterase in the absence of theophylline. In the platelets preincubated with Mitomycin C, thrombin-induced inhibition of adenyl cyclase, stimulation of membrane-bound cyclic AMP phosphodiesterase, and release of 250,000 dalton protein from platelet membranes were prevented. These results suggest that Mitomycin C will affect cellular membrane structure and function, and this extranuclear effect of Mitomycin C will lead to inhibition of aggregation in blood platelets.

Testosterone Potentiation of Ionophore and ADP Induced Platelet Aggregation : Relationship to Arachidonic Acid Metabolism

1981 ◽  
Vol 46 (02) ◽  
pp. 538-542 ◽  
Author(s):  
R Pilo ◽  
D Aharony ◽  
A Raz
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Unsaturated Fatty Acids ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Arachidonic Acid Metabolism ◽  
Ionophore A23187 ◽  
Low Concentrations ◽  
Induced Aggregation

SummaryThe role of arachidonic acid oxygenated products in human platelet aggregation induced by the ionophore A23187 was investigated. The ionophore produced an increased release of both saturated and unsaturated fatty acids and a concomitant increased formation of TxA2 and other arachidonate products. TxA2 (and possibly other cyclo oxygenase products) appears to have a significant role in ionophore-induced aggregation only when low concentrations (<1 μM) of the ionophore are employed.Testosterone added to rat or human platelet-rich plasma (PRP) was shown previously to potentiate platelet aggregation induced by ADP, adrenaline, collagen and arachidonic acid (1, 2). We show that testosterone also potentiates ionophore induced aggregation in washed platelets and in PRP. This potentiation was dose and time dependent and resulted from increased lipolysis and concomitant generation of TxA2 and other prostaglandin products. The testosterone potentiating effect was abolished by preincubation of the platelets with indomethacin.

The Increased Sensitivity of Platelets to Prostacyclin in Marathon Runners

1984 ◽  
Vol 51 (03) ◽  
pp. 385-387 ◽  
Author(s):  
Clive J Dix ◽  
David G Hassall ◽  
K Richard Bruckdorfer
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Cells ◽  
Platelet Aggregation ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Platelet Rich Plasma ◽  
Marathon Runners ◽  
Inhibition Of Platelet Aggregation ◽  
Increased Sensitivity ◽  
Membrane Bound

SummaryPlatelet-rich plasma was obtained 24 hr after the race ended from athletes who ran in the London marathon. The platelets were only marginally less sensitive to adrenaline than were those of non-runners using conventional aggregation tests. However, the runners’ platelets were much more sensitive to inhibition by prostacyclin, a prostaglandin synthesized by endothelial cells. It appeared that this effect was due to a greater activity in the platelets of the membrane-bound adenylate cyclase enzyme which generates intracellular cyclic AMP. Cyclic AMP production is known to be stimulated by prostacyclin and to cause the inhibition of platelet aggregation. The results indicate another possible protective effect of exercise against cardiovascular disease which is independent of the known changes in lipoprotein concentrations previously observed in athletes.

Effect of lanthanum on the inotropic response of isoproterenol: role of the superficially bound calcium

1985 ◽  
Vol 63 (9) ◽  
pp. 1106-1112 ◽  
Author(s):  
Ahmad B. Fawzi ◽  
John H. McNeill
Keyword(s):  
Cyclic Amp ◽  
Positive Inotropic Effect ◽  
Direct Action ◽  
Maximum Response ◽  
Inotropic Response ◽  
Guinea Pig Heart ◽  
Low Concentrations ◽  
Stimulation Of ◽  
Calcium Pool

Mammalian myocardial contractility is believed to be related to the amount of calcium contained in a highly labile superficial calcium pool. The purpose of this study was to determine the role of such sites in the positive inotropic effect of isoproterenol. Lanthanum, an ion that is restricted to the extracellular space and that displaces the superficially bound calcium, was selected as a tool for this investigation. In Langendorff preparations of the guinea pig heart, lanthanum decreased the basal contractility index (+ dP/dtmax) in a concentration-dependent fashion (0.05–3μM) and blocked the inotropic response of isoproterenol in a noncompetitive manner (0.25–3 μM). Three-micromolar lanthanum (i) reduced basal contractility and the maximum response to isoproterenol by 97 and 95%, respectively, (ii) had no significant effect (p > 0.05) on basal and isoproterenol-induced cyclic AMP levels, and (iii) had no effect on the Kd of [3H]nitrendipine binding, but reduced the Bmax by 31%. While 1 μM lanthanum reduced basal contractility and the maximum response to isoproterenol by 90 and 70%, respectively, it had no effect on [3H]nitrendipine binding. These results suggest that the effects of such low concentrations of lanthanum (≤3 μM) are not related to a direct action on the calcium channels and are not mediated by an inhibition of isoproterenol stimulation of the enzyme adenylate cyclase. Therefore, one interpretation of these results suggests that superficially bound calcium is required for the inotropic response of isoproterenol.

scholarly journals Abnormalities of factor VIII and platelet aggregation--use of ristocetin in diagnosing the von Willebrand syndrome

Blood ◽  
1975 ◽  
Vol 45 (3) ◽  
pp. 403-412 ◽  
Author(s):  
HJ Weiss
Keyword(s):  
Platelet Aggregation ◽  
Factor Viii ◽  
Platelet Rich Plasma ◽  
Second Phase ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Low Concentrations ◽  
Platelet Defects ◽  
Von Willebrand ◽  
Induced Aggregation

Ristocetin was used to study platelet aggregation in platelet-rich plasma and to assay the von Willebrand factor activity of factor VIII (VIII-VWF). Ristocetin-induced platelet aggregation (RIPA) was decreased in 13 of 18 patients with von Willebrand's disease (VWD) who had decreased plasma levels of VIII-VWF. The five patients with normal RIPA appeared to have mild VWD but did not constitute a separate subclass. RIPA was also abnormal in some patients with intrinsic platelet defects, but in no case was the defect corrected by normal plasma. The latter type of correction appears to be specific for VWD. Aspirin ingestion inhibited the second phase of RIPA (at low concentrations of ristocetin only) but did not affect the initial phase of aggregation or the level of VIII-VWF. We also studied a group of patients who had both abnormalities of the factor VIII complex and intrinsic platelet defects, such as impaired collagen-induced aggregation, as well. The findings in these patients and in those with typical von Willebrand's disease appear to comprise a spectrum of disorders (the von Willebrand syndrome) in which some abnormality of the factor VIII complex is associated with impaired platelet function. At present, ristocetin would appear to be a useful reagent for evaluating patients with bleeding disorders and for studying patients with the von Willebrand syndrome.

Different Effects of Aspirin, Dipyridamole and UD-CG 115 on Platelet Activation in a Model of Vascular Injury: Studies with Extracellular Matrix Covered with Endothelial Cells

1986 ◽  
Vol 56 (03) ◽  
pp. 333-339 ◽  
Author(s):  
A Eldor ◽  
I Vlodavsky ◽  
Z Fuks ◽  
T H Muller ◽  
W G Eisert
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Platelet Aggregation ◽  
Cyclic Amp ◽  
Platelet Activation ◽  
Platelet Rich Plasma ◽  
Thromboxane A2 ◽  
Phase Microscopy ◽  
Large Platelet ◽  
Platelet Aggregates

SummaryCultured endothelial cells produce an extracellular matrix (ECM) which activates platelets, similarly to deendothelialized vascular segments. Platelet-rich plasma (PRP) was incubated with endothelial cells cultures seeded in various densities on ECM. The interaction of the platelets with this artifical intima was evaluated by phase microscopy and by thromboxane A2 (TXA2) and prostacyclin (PGI2) measurement. Large platelet aggregates were formed on exposed ECM. Platelets aggregation but not adhesion on the ECM was markedly inhibited by the presence of endothelial cells. Pretreatment of the endothelial cells with 0.1 mM aspirin reduced their PGI2 synthesis and was associated with platelet aggregation on the ECM. 10 μM dipyridamole markedly inhibited platelet activation by ECM when the drug was added to citrated whole blood before PRP preparation. UD-CG 115 which elevates cyclic AMP in cardiac muscle, inhibited platelet aggregation and TXA2 production induced by ECM, in the presence as well as in the absence of endothelial cells, without any effect on endothelial PGI2 production.

Human Platelet Aggregation and Release Reaction Induced by Platelet Activating Factor (PAF-Acether) – Effects of Acetylsalicylic Acid and External Ionized Calcium

1985 ◽  
Vol 53 (02) ◽  
pp. 221-224 ◽  
Author(s):  
Marco Cattaneo ◽  
Maria Teresa Canciani ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Platelet Aggregation ◽  
Acetylsalicylic Acid ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Normal Subjects ◽  
Human Platelet Aggregation ◽  
Low Concentrations ◽  
Before And After ◽  
Platelet Secretion

SummaryThe effects of the cyclo-oxygenase inhibition on PAF-acether- induced human platelet aggregation and secretion are controversial. We studied the above parameters on citrated platelet-rich plasma of 12 normal subjects before and after the in vivo administration of acetylsalicylic acid (ASA). Individual sensitivities to PAF-acether were highly variable. ASA completely inhibited the platelet secretion induced by low concentrations of PAF-acether, but caused only partial inhibition when platelets were exposed to high concentrations of PAF-acether. The concentration of PAF-acether which overcame the cyclo-oxygenase inhibition varied substantially, depending on the individual sensitivity of the platelets to it. The addition of CaCl2 2 mM to the samples did not affect the extent of the platelet secretion, but increased irreversible aggregation in samples taken both before and after the ASA administration. These data suggest that low concentrations of PAF-acether stimulate the human platelet secretion by activating the cyclo-oxygenase pathway, whereas higher concentrations also trigger other mechanism(s) that suffice to induce human platelet secretion and full aggregation.

Studies on the Effect of Platelet Inhibitors on Platelet Adhesion to Collagen and Collagen-Induced Human Platelet Activation

1985 ◽  
Vol 53 (03) ◽  
pp. 337-342 ◽  
Author(s):  
S Krishnamurthi ◽  
V V Kakkar
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Platelet Adhesion ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Antiplatelet Agents ◽  
Calmodulin Antagonist ◽  
Release Reaction ◽  
Low Concentrations

SummaryThe effect of pyridoxal 5’-phosphate (PALP) and trifluoperazine (TFPZ), the calmodulin antagonist, on in vitro platelet adhesion to collagen and collagen-induced platelet activation was studied using platelet-rich-plasma (PRP) or washed platelets (WPL). Platelet aggregation and [14C]-5HT release induced by “threshold” or low concentrations of collagen (0.6 μg/ ml) in PRP were completely abolished by PALP (24 mM), TFPZ (250 μM) as well as indomethacin (10 μM). At higher concentrations of collagen (10–15 μg/ml) in PRP and WPL, the use of stirred and unstirred platelets treated with collagen enabled a distinction to be made between aggregation and adhesion- mediated release reaction. Platelet aggregation and the aggregation-mediated release reaction induced by these concentrations of collagen in stirred platelets were completely abolished by PALP, TFPZ and indomethacin although neither adhesion to collagen nor the adhesion-mediated release reaction of unstirred platelets was significantly affected by these inhibitors. Interestingly, both adhesion and the adhesion-mediated release reaction were abolished by concentrations of PALP 10–40 fold higher than those required to abolish aggregation. Collagen-induced platelet aggregation, but not platelet adhesion, was inhibited in resuspended platelets pretreated with PALP and NaBH4 indicating a separation in the membrane sites involved in aggregation and adhesion. The results further emphasize the distinction between adhesion and aggregation-mediated events with regards to collagen with the latter being more susceptible to inhibition by antiplatelet agents such as PALP and TFPZ.

Effects Of Soluble Immune Complexes From Diabetics On Platelet Aggregation And Release

1981 ◽  
Author(s):  
J Colwell ◽  
J Van Zile ◽  
M Kilpatrick ◽  
G Virella
Keyword(s):  
Platelet Aggregation ◽  
Immune Complexes ◽  
Platelet Rich Plasma ◽  
Gel Filtration ◽  
Atp Release ◽  
Diabetic Patients ◽  
Induce Platelet Aggregation ◽  
Low Concentrations ◽  
Soluble Immune Complexes ◽  
Polyethylene Glycol Precipitation

Soluble immune complexes (IC) can be detected in the serum of diabetic patients in frequencies ranging from 25 to 46%, depending on the screening technique used. Insulin-treated diabetics show a high frequency of insulin- anti-insulin IC (61% vs 4% in non-insulin treated patients) while other non-specific screening techniques show similar positivity frequencies in these two populations of diabetics. Soluble IC were isolated from the sera of 6 patients (5 under insulin treatment) using several combinations of polyethylene glycol precipitation, gel filtration and affinity chromatography. Sera from two normal donors was processed similarly and trace amounts of protein were recovered and used as controls. Platelet aggregation and release of ATP were studied with a Chronolog Lumi- aggregometer using platelet-rich plasma and low concentrations of ADP. All preparations of purified IC were found to induce platelet aggregation and ATP release of ADP sensitized platelets, while similarly obtained preparations from normal sera were inactive. Previous investigations had shown that sera from some diabetic patients contain factor(s) with platelet-activating properties. The present experiments suggest that soluble IC may be at least one of the factors.

Thiopental enhances human platelet aggregation by increasing arachidonic acid release

2001 ◽  
Vol 79 (10) ◽  
pp. 854-860 ◽  
Author(s):  
Rie Kitamura ◽  
Hideo Hirakata ◽  
Hiroto Okuda ◽  
Masami Sato ◽  
Hiroshi Toda ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Cytosolic Calcium ◽  
Free Calcium ◽  
Human Platelet Aggregation ◽  
Low Concentrations ◽  
Acid Release ◽  
Control Study

Conflicting results have been reported regarding the effect of thiopental on aggregation and cytosolic calcium levels in platelets. The present study attempted to clarify these phenomena. Using platelet-rich plasma or washed suspensions, platelet aggregation, thromboxane (TX) B2 formation, arachidonic acid (AA) release, and cytosolic free calcium concentrations ([Ca2+]i) were measured in the presence or absence of thiopental (30–300 µM). Platelet activation was induced by adenosine diphosphate (ADP, 0.5–15 µM), epinephrine (0.1–20 µM) arachidonic acid (0.5–1.5 mM), or (+)-9,11-epithia-11,12-methano-TXA2 (STA2, 30–500 nM). Measurements of primary aggregation were performed in the presence of indomethacin (10 µM). Low concentrations of ADP and epinephrine, which did not induce secondary aggregation in a control study, induced strong secondary aggregation in the presence of thiopental ([Formula: see text]100 µM). Thiopental ([Formula: see text]100 µM) also increased the TXB2 formation induced by ADP and epinephrine. Thiopental (300 µM) increased ADP- and epinephrine-induced 3H-AA release. Thiopental (300 µM) also augmented the ADP- and epinephrine-induced increases in [Ca2+]i in the presence of indomethacin. Thiopental appears to enhance ADP- and epinephrine-induced secondary platelet aggregation by increasing AA release during primary aggregation, possibly by the activation of phospholipase A2.Key words: barbiturates, anesthetics, eicosanoids, phospholipase.

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