The effects of an ASA-like hydroperoxide compound on adenosine diphosphate induced platelet aggregation

1984 ◽  
Vol 62 (3) ◽  
pp. 338-340
Author(s):  
J. J. F. Killackey ◽  
B. A. Killackey ◽  
I. Cerskus ◽  
R. B. Philp
Keyword(s):  
Platelet Aggregation ◽  
Acetylsalicylic Acid ◽  
Pharmacological Property ◽  
Human Platelet ◽  
Adenosine Diphosphate ◽  
Second Phase ◽  
Release Reaction ◽  
Human Platelet Aggregation ◽  
Second Phases ◽  
Induced Aggregation

A hydroperoxide compound structurally related to acetylsalicylic acid, 3-hydroperoxy-3-methylphthalide, inhibits both the first and second phases of adenosine diphosphate induced, biphasic, human platelet aggregation. This occurs over the same concentration range (0.05–0.5 mM) that acetylsalicylic acid inhibits second phase aggregation and the release reaction only. The complete inhibition of adenosine diphosphate induced aggregation is a unique pharmacological property for an acetylsalicylic-acid-like compound.

The Effect of Neuraminidase on Platelet Aggregation Induced by ADP, Norepinephrine, Collagen or Serotonin

1972 ◽  
Vol 28 (02) ◽  
pp. 221-227 ◽  
Author(s):  
James W. Davis ◽  
Kenneth T. N. Yue ◽  
Phyllis E. Phillips
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Second Phase ◽  
Acetylneuraminic Acid ◽  
Negative Surface ◽  
Negative Surface Charge ◽  
Second Phases ◽  
Induced Aggregation

SummaryIncubation of human platelet-rich plasma (PRP) with neuraminidase enhanced platelet aggregation induced by adenosine diphosphate (ADP), norepinephrine, collagen or serotonin. Both first and second phases of ADP- and norepinephrine -induced aggregation were enhanced. In two plasmas a second phase of ADP-induced aggregation occurred after incubation with neuraminidase, but not in the control preparations. In one plasma a second phase of serotonin-induced platelet aggregation occurred after incubation with neuraminidase. The incubation of PRP with exogenous N-acetylneuraminic acid (a product of the action of neuraminidase) had no effect on platelet aggregation. A possible explanation of the observed enhancement of platelet aggregation by neuraminidase is that the enzyme may have released sialic acid from platelet membranes and thereby reduced their net negative surface charge.

Evidence for Separate Mechanisms of Induction of the Platelet Release Reaction by Collagen and Adrenaline

1975 ◽  
Author(s):  
O. Tangen ◽  
S. Bygdeman
Keyword(s):  
Platelet Aggregation ◽  
Blood Clotting ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Second Phase ◽  
Release Reaction ◽  
Human Platelet Aggregation ◽  
Small Doses ◽  
Platelet Release ◽  
Induced Aggregation

The effect of some selected inhibitors of platelet release reaction and blood clotting on collagen- and adrenaline-induced human platelet aggregation was investigated by means of the turbidimetric method according to Born. Acetylsalicylic acid (ASA) inhibited both collagen- and adrenaline-induced platelet aggregation in citrated platelet rich plasma (PRP). Addition of sufficient amounts of Ca++ to give concentrations similar to those in native blood suppressed the inhibition by small doses of ASA (5–10 μg/ml) on collagen-induced aggregation and the second phase of adrenaline-induced aggregation. Higher concentrations of ASA (13–30 μg/ml) could partly overcome this effect of Ca++. Heparin, which had no effect on primary adenosine diphosphate (ADP)-induced aggregation, inhibited platelet aggregation induced by collagen. In contrast, both the first and second phase of adrenaline-induced aggregation was markedly potentiated by heparin. Dextran sulphate had effects basically similar to heparin, Nicotinic acid inhibited collagen-induced aggregation, but had no effect on the second phase of adrenaline-induced aggregation. These results indicate that the platelet release reaction induced by collagen and adrenaline is mediated via separate receptors or reaction pathways.

Thrombin Interaction with Human Platelets Potentiation of Thrombin-induced Aggregation and Release by Inactivated Thrombin

1974 ◽  
Vol 32 (01) ◽  
pp. 207-215 ◽  
Author(s):  
David R. Phillips
Keyword(s):  
Platelet Aggregation ◽  
Binding Sites ◽  
Human Platelet ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Induce Platelet Aggregation ◽  
Release Reaction ◽  
Proteolytic Site ◽  
Induced Aggregation ◽  
Inhibited Enzyme

SummaryThe possibility that thrombin acts on platelets by a mechanism other than proteolysis was investigated. The proteolytic site of thrombin was modified with phenylmethylsulfonyl fluoride (PMSF). This modified enzyme did not induce platelet aggregation or the platelet release reaction. Platelets were then incubated with the inactivated enzyme (PMS-thrombin) and later with active thrombin. In this sequence of incubation, PMS-thrombin enhanced not only platelet aggregation induced by active thrombin but also the thrombin-induced release reaction. Preincubation with PMS-thrombin was essential for this enhancement as the inhibited enzyme did not affect aggregation if added after active thrombin. The effect of PMS-thrombin was limited to thrombin-induced reactions of the platelet. The inhibited enzyme had no effect on aggregation induced by adenosine diphosphate or collagen, or on thrombininduced coagulation of fibrinogen. These results suggest (1) that both proteolytic and binding sites for thrombin are present on the human platelet plasma membrane ; and (2) that interaction of thrombin with the binding site potentiates the activity of the proteolytic site.

scholarly journals Adenosine Diphosphate Induced Aggregation and Release Reaction in Heparinized Platelet Rich Plasma

1977 ◽  
Author(s):  
S. Heptinstall ◽  
G.P. Mulley
Keyword(s):  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Exchange Chromatography ◽  
Second Phase ◽  
Release Reaction ◽  
Ionised Calcium ◽  
Irreversible Aggregation ◽  
Induced Aggregation ◽  
Citrate Release

Preparations of heparinized platelet rich plasma (PRP) from 54 different volunteers were examined to determine the extent of platelet aggregation and release reaction both in the absence and presence of citrate. Platelet aggregation was studied in fresh untreated samples of PRP using a range of concentrations of ADP. To study release reaction platelets in a portion of each preparation were labelled with 3H-5-hydroxytryptamine. Released radioactivity was measured after stirring with ADP or with ADP and citrate.Even in the absence of citrate release was considerable in 26 of the preparations. There was a good correlation between extent of aggregation and extent of release reaction. When second phase aggregation occurred release was extensive, when release was low or absent the higher concentrations of ADP were required to bring about “irreversible” aggregation. Whenever citrate was present release reaction was enhanced. Enhanced release reaction was also observed in PRP in which the bulk of plasma calcium had been exchanged for sodium by ion exchange chromatography.It is concluded that ADP induced release reaction can occur in heparinized PRP but that it is enhanced by reducing the concentration of extracellular ionised calcium.

scholarly journals The Effect of Imidazole on Human Platelet Aggregation

Blood ◽  
1971 ◽  
Vol 38 (4) ◽  
pp. 417-421 ◽  
Author(s):  
JAMES W. DAVIS ◽  
PHYLLIS E. PHILLIPS
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Glass Bead ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Second Phase ◽  
Platelet Function Tests ◽  
Human Platelet Aggregation ◽  
Function Tests ◽  
Induced Aggregation

Abstract Since imidazole buffers have been used in platelet function tests and the compound has been reported to alter several biochemical activities of platelets, it seemed important to determine whether imidazole influenced platelet aggregation. ADP-induced, collagen-induced, and norepinephrine-induced platelet aggregations were tested in platelet-rich plasma by turbidimetric techniques. Glass bead-induced platelet aggregation in whole blood was tested by a method dependent upon platelet counts. Imidazole, in concentrations of 5mM or less, inhibited aggregation induced by each of these four agents and had negligible effect on the pH of platelet-rich plasma. The second phase of both ADP- and norepinephrine-induced aggregation was inhibited or abolished by imidazole, and 5mM imidazole also inhibited the first phase of norepinephrine-induced aggregation. As little as 0.5 mM imidazole inhibited collagen-induced aggregation in some plasmas. Imidazole appears to be unsuitable for use as a buffer in platelet function tests.

Sevoflurane Inhibits Human Platelet Aggregation and Thromboxane A2Formation, Possibly by Suppression of Cyclooxygenase Activity

1996 ◽  
Vol 85 (6) ◽  
pp. 1447-1453. ◽  
Author(s):  
Hideo Hirakata ◽  
Fumitaka Ushikubi ◽  
Hiroshi Toda ◽  
Kumi Nakamura ◽  
Satoko Sai ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Human Platelet ◽  
Adenosine Diphosphate ◽  
Scatchard Analysis ◽  
Cyclooxygenase Activity ◽  
Human Platelet Aggregation ◽  
Induced Aggregation

Background Halothane increases bleeding time and suppresses platelet aggregation in vivo and in vitro. A previous study by the authors suggests that halothane inhibits platelet aggregation by reducing thromboxane (TX) A2 receptor-binding affinity. However, no studies of the effects of sevoflurane on platelet aggregation have been published. Methods The effects of sevoflurane, halothane, and isoflurane were examined at doses of 0.13-1.4 mM. Human platelet aggregation was induced by adenosine diphosphate, epinephrine, arachidonic acid, prostaglandin G2, and a TXA2 agonist ([+]-9, 11-epithia-11, 12-methano-TXA2, STA2) and measured by aggregometry. Platelet TXB2 levels were measured by radioimmunoassay, and the ligand-binding characteristics of the TXA2 receptors were examined by Scatchard analysis using a [3H]-labeled TXA2 receptor antagonist (5Z-7-(3-endo-([ring-4-[3H] phenyl) sulphonylamino-[2.2.1.] bicyclohept-2-exo-yl) heptenoic acid, [3H]S145). Results Isoflurane (0.28-0.84 mM) did not significantly affect platelet aggregation induced by adenosine diphosphate and epinephrine. Sevoflurane (0.13-0.91 mM) and halothane (0.49-1.25 mM) inhibited secondary platelet aggregation induced by adenosine diphosphate (1-10 microM) and epinephrine (1-10 microM) without altering primary aggregation. Sevoflurane (0.13 mM) also inhibited arachidonic acid-induced aggregation, but not that induced by prostaglandin G2 or STA2, although halothane (0.49 mM) inhibited the latter. Sevoflurane (3 mM) did not affect the binding of [3H]S145 to platelets, whereas halothane (3.3 mM) suppressed it strongly. Sevoflurane (0.26 mM) and halothane (0.98 mM) strongly suppressed TXB2 formation by arachidonic acid-stimulated platelets. Conclusions The findings that sevoflurane suppressed the effects of arachidonic acid, but not those of prostaglandin G2 and STA2, suggest strongly that sevoflurane inhibited TXA2 formation by suppressing cyclooxygenase activity. Halothane appeared to suppress both TXA2 formation and binding to its receptors. Sevoflurane has strong antiaggregatory effects at subanesthetic concentrations (greater than 0.13 mM; i.e., approximately 0.5 vol/%), whereas halothane has similar effects at somewhat greater anesthetic concentrations (0.49 mM; i.e., approximately 0.54 vol/%). Isoflurane at clinical concentration (0.84 mM; i.e., approximately 1.82 vol/%) does not affect platelet aggregation significantly.

Ticlopidine Facilitates the Deaggregation of Human Platelets Aggregated by Thrombin

1994 ◽  
Vol 71 (01) ◽  
pp. 091-094 ◽  
Author(s):  
M Cattaneo ◽  
B Akkawat ◽  
R L Kinlough-Rathbone ◽  
M A Packham ◽  
C Cimminiello ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Platelet Aggregation ◽  
Prostaglandin E1 ◽  
Human Platelet ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Before And After ◽  
Normal Human ◽  
Platelet Aggregates ◽  
Induced Aggregation

SummaryNormal human platelets aggregated by thrombin undergo the release reaction and are not readily deaggregated by the combination of inhibitors hirudin, prostaglandin E1 (PGE1) and chymotrypsin. Released adenosine diphosphate (ADP) plays an important role in the stabilization of thrombin-induced human platelet aggregates. Since ticlopidine inhibits the platelet responses to ADP, we studied thrombin-induced aggregation and deaggregation of 14C-serotonin-labeled platelets from 12 patients with cardiovascular disease before and 7 days after the oral administration of ticlopidine, 250 mg b.i.d. Before and after ticlopidine, platelets stimulated with 1 U/ml thrombin aggregated, released about 80–90% 14C-serotinin and did not deaggregate spontaneously within 5 min from stimulation. Before ticlopidine, hirudin (5× the activity of thrombin) and PGE1 (10 μmol/1) plus chymotrypsin (10 U/ml) or plasmin (0.06 U/ml), added at the peak of platelet aggregation, caused slight or no platelet deaggregation. After ticlopidine, the extent of platelet deaggregation caused by the same inhibitors was significantly greater than before ticlopidine. The addition of ADP (10 μmol/1) to platelet suspensions 5 s after thrombin did not prevent the deaggregation of ticlopidine-treated platelets. Thus, ticlopidine facilitates the deaggregation of thrombin-induced human platelet aggregates, most probably because it inhibits the effects of ADP on platelets.

scholarly journals Inhibition of platelet aggregation by protease inhibitors. Possible involvement of proteases in platelet aggregation

Blood ◽  
1978 ◽  
Vol 52 (1) ◽  
pp. 1-12 ◽  
Author(s):  
N Aoki ◽  
K Naito ◽  
N Yoshida
Keyword(s):  
Platelet Aggregation ◽  
Protease Inhibitors ◽  
Serine Proteases ◽  
Human Platelet ◽  
Serotonin Release ◽  
Second Phase ◽  
Inhibition Of Platelet Aggregation ◽  
Naturally Occurring ◽  
Human Platelet Aggregation ◽  
Platelet Receptor

Abstract The possible participation of proteases in human platelet aggregation was explored using various protease inhibitors and substrates. Protease inhibitors used included naturally occurring inhibitors of serine proteases and synthetic inhibitors that modify the active site of protease. Substrates used were synthetic substrates for the trypsin type as well as for the chymotrypsin type of protease. All these inhibitors and substrates inhibited platelet aggregation and serotonin release induced by ADP, collagen, epinephrine, or thrombin. In ADP- and epinephrine-induced platelet aggregation the second phase of aggregation was most efficiently inhibited. The inhibitors suppressed the formation of malondialdehyde during platelet aggregation. Release by aggregating agents of arachidonate and its metabolites from indomethacin-treated platelets as well as nontreated platelets was also inhibited. The inhibitors apperar to interact with stimulated platelets but not with unstimulated platelets. These observations suggest that the interaction of an aggregating agent with its platelet receptor activates a unique precursor serine protease that in turn activates platelet phospholipase to liberate arachidonic acid (the precursor of the potent platelet aggregating agent thromboxane A2) from platelet phospholipids.

Inhibition of Human and Rat Platelet Aggregation by Extracts of Mo-er (Auricularia auricula)

1982 ◽  
Vol 48 (02) ◽  
pp. 162-165 ◽  
Author(s):  
K C Agarwal ◽  
F X Russo ◽  
R E Parks
Keyword(s):  
Platelet Aggregation ◽  
Cyclic Amp ◽  
Human Platelet ◽  
Rapid Onset ◽  
Hot Water ◽  
Inhibitory Effects ◽  
Inhibition Of Platelet Aggregation ◽  
Auricularia Auricula ◽  
Human Platelet Aggregation ◽  
Induced Aggregation

SummaryHot water extracts of Mo-er (1 gm by 15 ml of water), an oriental food (Auricularia auricula), inhibit strongly both human and rat platelet ADP-induced aggregation. HPLC analysis of two varieties of Mo-er, A.auricula and A.polytricha (a black tree fungus), shows that they contain adenosine (Ado), 133 and 154 micrograms per gram of dry fungus, respectively. The inhibition of ADP-induced platelet aggregation by Mo-er extracts and by Ado was compared. Mo-er extracts caused a more rapid onset and a longer duration of inhibition than produced by equivalent amounts of Ado. Furthermore, Mo-er extract treated with adenosine deaminase to degrade the Ado retained the capacity to inhibit platelet aggregation. The inhibitory effects of Mo-er extracts on ADP-induced human platelet aggregation are greatly potentiated by the inhibitors of cyclic AMP phosphodiesterase such as oxagrelate (phthalazinol) and papaverine. The inhibition of platelet aggregation is only partially blocked by 2’,5’-dideoxy-adenosine (DDA), an inhibitor of platelet adenylate cyclase and 5’-deoxy, 5’-methylthioadenosine (MTA), an antagonist of Ado receptors. ADP-induced rat platelet aggregation is strongly inhibited by Mo-er extracts, but not by Ado. This inhibition is not reversed by either DDA or MTA. These findings indicate that Mo-er extracts contain an agent (or agents) in addition to Ado, that blocks platelet aggregation by a mechanism that does not involve the platelet cyclic AMP system.

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