Thapsigargin Induces Platelet Aggregation, thereby Releases Lactate Dehydrogenase from Rat Platelets

SummaryA major limitation to single-cell protein (SCP) as a human food is its high nucleic acid content, the purine moiety of which is metabolised to uric acid. Rats given a Fusarium mould as a source of SCP in diets containing oxonate, a uricase inhibitor, showed elevated plasma and kidney uric acid concentrations after 21 d, which were related to the level of dietary mould. ADP-induced and thrombin-induced platelet aggregation was greater in the hyperuricaemic rats than in controls and a progressive increase in aggregation with increasing levels of dietary mould was observed. Furthermore a time-lag, exceeding the life-span of rat platelets, was observed between the development of hyperuricaemia and the increase in aggregation. A similar time-lag was observed between the lowering of the hyperuricaemia and the reduction of platelet aggregation when oxonate was removed from the diet.If human platelets react to uric acid in the same manner as rat platelets this might explain the link that has been suggested between hyperuricaemia and ischaemic heart disease. In that event diets high in nucleic acids might be contra-indicated in people at risk from ischaemic heart disease.In rats given a low protein diet (50 g casein/kg) for 21 d ADP-induced and thrombin-induced platelet aggregation and whole blood platelet count were reduced compared with control animals receiving 200 g casein/kg diet but not in rats given 90 or 130 g casein/kg diet. A study of the time course on this effect indicated that the reduction both in aggregation tendency and in whole blood platelet count occurred after 4 d of feeding the low protein diet. These values were further reduced with time.

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Ticlopidine and Clopidogrel (SR 25990C) Selectively Neutralize ADP Inhibition of PGE1-Activated Platelet Adenylate Cyclase in Rats and Rabbits

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647481 ◽

1991 ◽

Vol 65 (02) ◽

pp. 186-190 ◽

Cited By ~ 61

Author(s):

G Defreyn ◽

C Gachet ◽

P Savi ◽

F Driot ◽

J P Cazenave ◽

...

Keyword(s):

Platelet Aggregation ◽

Adenylate Cyclase ◽

Direct Effect ◽

Cyclic Nucleotide ◽

Camp Accumulation ◽

Rabbit Platelets ◽

Camp Levels ◽

Kinetics Of ◽

Camp Elevation ◽

Rat Platelets

SummaryTiclopidine and its potent analogue, clopidogrel, are powerful inhibitors of ADP-induced platelet aggregation. In order to improve the understanding of this ADP-selectivity, we studied the effect of these compounds on PGE1-stimulated adenylate cyclase and on the inhibition of this enzyme by ADP, epinephrine and thrombin. Neither drug changed the basal cAMP levels nor the kinetics of cAMP accumulation upon PGEj-stimulation in rat or rabbit platelets, which excludes any direct effect on adenylate cyclase or on cyclic nucleotide phosphodiesterase. However, the drop in cAMP levels observed after addition of ADP to PGEr stimulated control platelets was inhibited in platelets from treated animals. In contrast, the drop in cAMP levels produced by epinephrine was not prevented by either drug in rabbit platelets. In rat platelets, thrombin inhibited the PGEX-induced cAMP elevation but this effect seems to be entirely mediated by the released ADP. Under these conditions, it was not surprising to find that clopidogrel also potently inhibited that effect of thrombin on platelet adenylate cyclase. In conclusion, ticlopidine and clopidogrel selectively neutralize the ADP inhibition of PGEr activated platelet adenylate cyclase in rats and rabbits.

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Formation of Prostaglandin Cyclo-Peroxides and Prostaglandins by Phospholipase A2 in Platelets of Normal and Essential Fatty Acid Deficient Rats

10.1055/s-0039-1680762 ◽

1977 ◽

Author(s):

J.E. Vincent ◽

F.J. Zijlstra

Keyword(s):

Fatty Acid ◽

Platelet Aggregation ◽

Phospholipase A2 ◽

Essential Fatty Acid ◽

Essential Fatty Acid Deficient ◽

Incubation Periods ◽

Rat Platelets

Phospholipase A2 has a biphasic action upon rat platelet aggregation, enhancing after shorter and inhibiting after longer incubation periods. The first effect is inhibited by indomethacin.Cycloperoxides and thromboxane-like substances and prostaglandins are formed on incubation with the enzyme in the same amounts whether aggregation is induced or not. Formation of cycloperoxides and thromboxanes is not leading to aggregation. Phospholipase A2 enhances the aggregation of the platelets of essential fatty acid deficient rats. Only very small amounts of cycloperoxides and thromboxane-like substances are formed. It is concluded that cycloperoxides and thromboxanes can enhance, but not induce aggregation in rat platelets.

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Platelet Antiaggregating Activity and Chemical Constituents of Salvia x Jamensis J. Compton

Natural Product Communications ◽

10.1177/1934578x0800300611 ◽

2008 ◽

Vol 3 (6) ◽

pp. 1934578X0800300 ◽

Cited By ~ 6

Author(s):

Angela Bisio ◽

Giovanni Romussi ◽

Eleonora Russo ◽

Nunziatina De Tommasi ◽

Nicola Mascolo ◽

...

Keyword(s):

Data Analysis ◽

Platelet Aggregation ◽

Ursolic Acid ◽

Betulinic Acid ◽

Spectroscopic Data ◽

Chemical Constituents ◽

Isopimaric Acid ◽

Phytochemical Study ◽

Rat Platelets ◽

Significant Concentration

A phytochemical study has been carried out on the surface exudate of Salvia x jamensis, which showed a significant platelet antiaggregating activity. The known compounds isopimaric acid (2), 14-α-hydroxy-isopimaric acid (3), 3β-hydroxy-isopimaric acid (4), 7,8β-dihydrosalviacoccin (5), betulinic acid (6), and ursolic acid (7) were isolated together with the new diterpene 1. The structure of 1 was determined as 15,16-epoxy-cleroda-3-en-7α,10β-dihydroxy-12,17;19,18-diolide on the basis of spectroscopic data analysis. Among all tested compounds, 2 showed a significant concentration-dependent antiaggregating activity when ADP (3 μM) was used as agonist on rat platelets. Conversely, 1 increased ADP–induced platelet aggregation.

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Aggregation and release in thrombocytes of the duck

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1975.229.1.206 ◽

1975 ◽

Vol 229 (1) ◽

pp. 206-210 ◽

Cited By ~ 12

Author(s):

RA Stiller ◽

FA Belamarich ◽

D Shepro

Keyword(s):

Acid Phosphatase ◽

Platelet Aggregation ◽

Lactate Dehydrogenase ◽

Adenine Nucleotides ◽

Intracellular Enzyme ◽

Release Reaction ◽

No Release ◽

Metabolic Pool ◽

Enzyme Markers ◽

Induced Aggregation

Avian thromboyctes are aggregated by a number of substances that cause platelet aggregation, and evidence suggests that this response is related to the release of serotonin (5-hydroxytryptamine, 5-HT) from intracellular granules. In this study duck thrombocytes released 5-HT during collagen-induced aggregation, but thrombocytes incubated with 14C-labeled adenine did not release radioactive adenine nucleotides. These results indicate the existence of a metabolic pool of adenine nucleotides that is separate from released constituents of the cell. No unlabeled adenine compounds were detected in the supernatants of aggregated thrombocytes indicating either the rapid alteration of released nucleotides or the absence of a specific release pool of adenine nucleotides. Finally there is no release of the intracellular enzyme markers, lactate dehydrogenase, beta-glucuronidase, and acid phosphatase, during collagen-induced aggregation. These findings suggest that avian thrombocytes exhibit a specific release reaction and that serotonin acts as the functional counterpart of ADP in platelet aggregation.

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Anti-platelet aggregation effects of extracts from Arbutus unedo leaves

Plant Science Today ◽

10.14719/pst.2017.4.2.298 ◽

2017 ◽

Vol 4 (2) ◽

pp. 68 ◽

Cited By ~ 3

Author(s):

Mohammed El Haouari ◽

Hassane Mekhfi

Keyword(s):

Platelet Aggregation ◽

Initial Rate ◽

Ethyl Acetate Extract ◽

Traditional Use ◽

Arbutus Unedo ◽

Diethyl Ether Extract ◽

Ic50 Values ◽

Different Doses ◽

Rat Platelets

It is well known that platelet hyperactivity is a risk factor for cardiovascular diseases such as atherosclerosis, stroke and myocardial infarction. This study aimed to examine the effects of extracts enriched in flavonoids obtained from Arbutus unedo leaves on platelet aggregation. Rat platelets were prepared and incubated in vitro with different doses of the tested extracts, and aggregation was trigged by physiological agonists. Platelet treatment with increasing concentrations (0.1 - 1 mg/ml) of diethyl ether extract (genins = free flavonoids) or ethyl acetate extract (hetrosidic flavonoids) inhibited platelet aggregation evoked by thrombin in a concentration-dependant manner. The IC50 values were 0.22 ± 0.03 and 0.36 ± 0.05 mg/ml for genins and heterosidic flavonoids respectively. Treatment with Arbutus unedo extracts also significantly reduced the initial rate of platelet aggregation. At 1 mg/ml, the rate inhibition was 97.8 ± 0.74 and 90.8 ± 1.55 % for genins and heterosidic flavonoids respectively. In addition, flavonoids significantly inhibited platelet aggregation induced by ADP, collagen or epinephrine. We conclude that Arbutus unedo extracts show antiaggregant effects due mainly to flavonoids. These results may partly explain the traditional use of Arbutus unedo leaves for the treatment of cardiovascular disorders such as hypertension.

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Decrease Of Platelet Aggregation In Rats Under Gastric Ulcer-Causing Stress

10.1055/s-0038-1653308 ◽

1981 ◽

Author(s):

T Terano ◽

T Hamazaki ◽

A Hirai ◽

Y Tamura ◽

A Kumagai

Keyword(s):

Gastric Ulcer ◽

Platelet Aggregation ◽

Room Temperature ◽

Platelet Rich Plasma ◽

Water Immersion ◽

Ether Anesthesia ◽

Normal Rat ◽

Antiaggregatory Activity ◽

Stomach Ulceration ◽

Rat Platelets

Decreased platelet aggregability may play an important role in gastric ulcer continuation. We attempted to identify an antiaggregatory substance involved in stress induced gastric ulceration in rats. METHODS: 1) Male SD rats (180-220g) were stressed by water immersion, one group for 30 min and another for 120 min. Platelet rich plasma (PRP) and platelet poor plasma (PPP) were obtained from stressed rats and normal rats under ether anesthesia. Platelet aggregation was carried out by addition of 1/10 vol of 50μM ADP and was measured using a Sienco aggregometer. 2) Platelet-plasma mixing experiments. PRP from normal rats and from rats stressed for 30 min was centrifuged and the supernatant was discarded. Packed platelets from normal rats were resuspended in PPP from stressed rats and platelets from stressed rats were resuspended in PPP from normal rats. Also, platelets from each rat were resuspended in PPP of the same rat. Aggregation was then observed. 3) Stability tests of the activity in PPP from stressed rats which depressed platelet aggregation. PPP from normal and stressed rats was stored for 4. hr either in ice or at room temperature. Platelets from a normal rat were then mixed with each PPP. 4) 6 keto PGF1α was measured by RIA. RESULTS: 1) The aggregability of rat platelets was decreased to 1/4-1/5 and to 1/10 of the normal value, after 30 min and 120 min stress, respectively. 2) Normal platelets suspended in PPP from stressed rats did not aggregate. Platelets from stressed rats suspended in normal PPP showed significant aggregability. 3) The antiaggregatory activity of PPP from stressed rats was lost significantly after storage at room temperature for 4 hr, while storage in ice did not greatly affect this activity. DISCUSSION: During water immersion stress which causes stomach ulceration of rats there appear platelet antiaggregatory substance(s) in plasma. Like PGI2, the substance observed in this experiment is more stable at 0°C than at room temperature. However, plasma 6 keto PGF1αconcentrations in stressed rats did not increase enough to explain the decreased platelet aggregation. Identification of this antiaggregatory substance is now under way.

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Evidence for 1,25-dihydroxycholecalciferol (l,25-(OH)2D3) as a proaggregating agent in rat and human platelets

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y83-143 ◽

1983 ◽

Vol 61 (8) ◽

pp. 954-955 ◽

Cited By ~ 3

Author(s):

D. E. Agwu ◽

B. J. Holub

Keyword(s):

Platelet Aggregation ◽

Platelet Activation ◽

Human Platelets ◽

Calcium Mobilization ◽

Biological Role ◽

Calcium Availability ◽

Rat Platelets

In view of the established biological role for 1,25-dihydroxycholecalciferol (DHCC) in calcium mobilization and the significance of calcium availability in platelet activation, it was of interest to investigate the potential for DHCC to act as a proaggregating agent. The present results provide evidence that DHCC at a concentration of 0.01 μg/µL can both aggregate human platelets and potentiate ADP-induced platelet aggregation. DHCC was also capable of aggregating rat platelets.

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Enhancement by ADP of Thrombin-induced Aggregation in ADP-refractory Platelets

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647784 ◽

1973 ◽

Vol 29 (02) ◽

pp. 445-449 ◽

Cited By ~ 3

Author(s):

Nicole Simard-Duquesne

Keyword(s):

Platelet Aggregation ◽

Adp Release ◽

Induced Aggregation ◽

Rat Platelets

SummaryIn ADP-refractory rat platelets, thrombin-induced aggregation is enhanced in the presence of ADP and inhibited in the absence of ADP. Two mechanisms are proposed for thrombin-induced platelet aggregation: one through ADP release which may become refractory, and a second mechanism in which thrombin acts synergistieally with ADP.

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Species-Dependent Inhibition of Platelet Aggregation by Adenosine and Dipyridamole: Paradoxical Potentiation in the Rat

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654127 ◽

1970 ◽

Vol 23 (01) ◽

pp. 129-139 ◽

Cited By ~ 6

Author(s):

R. B Philp ◽

B Bishop ◽

Keyword(s):

Platelet Aggregation ◽

Guinea Pig ◽

Adenosine Receptors ◽

Guinea Pigs ◽

Human Subjects ◽

Adenosine Diphosphate ◽

Inhibition Of Platelet Aggregation ◽

Rabbit Platelets ◽

Dependent Inhibition ◽

Rat Platelets

SummaryPlatelets of cats, rabbits, guinea pigs, rats and human subjects were aggregated with adenosine diphosphate after having been in contact with adenosine or dipyridamole for 5 to 60 min. The species profiles of both agents were the same. Both inhibited aggregation of human and rabbit platelets and the degree of inhibition increased with the time of contact. Neither inhibited aggregation of cat or guinea-pig platelets and both potentiated the rate and extent of aggregation of rat platelets: the degree of potentiation increased with the time of contact. Some reports on the related effects of adenosine and dipyridamole are reviewed and it is suggested that the effects of dipyridamole might be due to an affinity for adenosine receptors.

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