scholarly journals Arachidonic Acid Metabolism of Platelet in Diabetes

1977 ◽  
Author(s):  
T. Kurosawa ◽  
T. Tojima ◽  
H. Funayama ◽  
Y. Takahashi ◽  
Y. Shiokawa
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Sodium Citrate ◽  
Acid Metabolism ◽  
Platelet Rich Plasma ◽  
Normal Subjects ◽  
Arachidonic Acid Metabolism ◽  
Gas Liquid Chromatography ◽  
Glucose Loading ◽  
Freeze Dried

Recent reports have indicated that platelet aggregation is enhanced in some diabetics who have proliferative retinopathy and that platelet function is a altered by glucose loading. But the mechanism is not clarified yet. Arachidonic acid, the precursor of prostaglandin endoperoxide, plays a major role on platelet aggregation. Blood samples were collected with sodium citrate at 0, 30, 60, 120 and 300 minutes after 100 g glucose loading. Platelet-rich plasma was obtained by centrifugation and platelet aggregation was studied photometrically adding ADP. Platelet was obtained by further centrifugation and was kept freeze-dried. Platelet samples were extracted and transesterificated and separated by gas liquid chromatography. The quantitative regulation of arachidonic acid in platelets was measured by the composition ratio of arachidonic acid (C20-4)/linoleic acid (C18-2)=AL index. The results of platelet aggregation after glucose loading were as follows; platelet aggregation was not changed remarkably in normal subjects, but was enhanced at 30 and 60 and suppressed at 120 minutes in diabetics.AL index is as fol lows:prior to glucose loading, AL index of diabetics (4.6 ± 1.2) was higher than that of normal subjects (3.5 ± 0.5). After glucose loading, no significant change was observed in normal subjects, but AL index was increased at 30 (4.8 ± 1.4) and 60 (4.9 ± 1.4) and decreased at 120 minutes (4.1 ± 0.9) in diabetics. The results indicates that there is a certain relationship between quantitative regulation of arachidonic acid in platelet and platelet aggregation and that hyperaggregation may be induced by abnormal prostaglandin metabolism in diabetes.

CYCLOOXYGENASE AND LIPOXYGENASE PRODUCTS SYNERGISTICALLY MODULATE TUMOR CELL INDUCED PLATELET AGGREGATION

1987 ◽  
Author(s):  
Bruce W Steinert ◽  
James M Onoda ◽  
Bonnie F Sloane ◽  
John D Taylor ◽  
Kenneth V Honn
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Tumor Cell ◽  
Acid Metabolism ◽  
Platelet Rich Plasma ◽  
Arachidonic Acid Metabolism ◽  
Cyclooxygenase Inhibitors ◽  
Dependent Manner ◽  
Lipoxygenase Inhibitors ◽  
Agonist Concentration

There has been considerable controversy surrounding the ability of inhibitors of arachidonic acid metabolism to concomitantly inhibit tumor cell induced platelet aggregation (TCIPA). Reconciliation of this controversy has been difficult due to the wide variability of experimental conditions (e.g., inhibitor concentration, strength of the inducing agonist).In the present study, we examined the effects of several cyclooxygenaseand lipoxygenase inhibitors on the induction of platelet aggregation by Walker 256 carcinosarcoma (W256) cells. We have previously demonstrated that aggregation of platelet rich plasma (PRP), induced by W256 cells, was initiated via a thrombin dependent mechanism. Platelet aggregation was induced by the addition of W256 cells (75,000-J500,000 cells/cuvette) to rat PRP preincubated with inhibitor(s) or diluent. The strength of the inducing stimulus affected both the degree of aggregation and the production of thromboxane A2 (TXA2) in a dose dependent manner. A weak stimulus (low concentration of W256 cells) produced only a low level of aggregation and low TXA2 production, whereas aggregation induced by a strong stimulus (high concentration of W256 cells) resulted in significant aggregation and increased TXA2 production. Preincubation (5 min., 37°C) of rat PRP with cyclooxygenase inhibitors (e.g., aspirin, indomethacin, ibuprofen) resulted in complete inhibition of platelet aggregation at low agonist concentration (75,000 W256 cells), whereas when a high agonist concentration (500,000 W256 cells) was used to induce aggregation, the inhibitors failed to inhibit TCIPA. The addition of fewer than 50,000W256 cells failed to induce any measurable platelet aggregation in the presence or absence of inhibitors. TCIPA was not affected by lipoxygenaseinhibitors (e.g.,quercetin) alone regardless of agonist concentration. Both cyclooxygenase and lipoxygenase inhibitors, however, were required to significantly inhibit TCIPA induced by high agonist concentration. Compounds which inhibited both the cycloogygenase and lipoxygenase pathways (e.g.,hydroquinone, BW755c) inhibited TCIPA at all agonist concentrations. Nafazatrom failed to inhibit TCIPA consistant with a lack of effect on platelet cyclooxygenase and lipoxygenase. Therefore, we conclude cyclooxygenase (e.g., TXA2) and lipoxygenase (e.g., 12-HETE) products of platelet arachidonic acid metabolism and the strength of the inducingagonist are important criteria in TCIPA. This study may help to clarify the current controversy regarding the inhibition of TCIPA by inhibitors of arachidonic acid metabolism.

scholarly journals Effects of elastase on platelet aggregation and it's arachidonic acid metabolism in normal subjects.

1985 ◽  
Vol 16 (3) ◽  
pp. 294-297 ◽  
Author(s):  
Shigeki SENSAKI ◽  
Tateo SUGIYAMM ◽  
Kenji KANAJI ◽  
Fumitaka USHIKUBI ◽  
Minoru OKUMA ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Acid Metabolism ◽  
Normal Subjects ◽  
Arachidonic Acid Metabolism

Human Platelet Aggregation Induced by the Synthetic Endoperoxide Analogue U-46619 is Independent From Secretion, Prostaglandin Production and Extracellular Calcium

1979 ◽  
Author(s):  
G. Di Minno ◽  
L. Bianchi ◽  
G. de Gaetano ◽  
M.J. Silver
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Acid Metabolism ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Arachidonic Acid Metabolism ◽  
Extracellular Calcium ◽  
Reversible Aggregation ◽  
Human Platelet Aggregation ◽  
Aspirin Ingestion

U-46619 is a stable analogue of cyclic prostaglandin endoperoxides which induces human platelet aggregation independently from nucleotide secretion. We studied platelet aggregation, 14C-5 HT release and malondialdehyde (MDA) production induced by this compound in stirred or unstirred platelet-rich plasma (PRP) samples from 11 healthy volunteers. Each subject was tested both before and 90 min after aspirin ingestion (500 mg). The threshold aggregating concentration (TAC) of U-466l9 ranged between 240 and 900 nM. Aggregation was maximal between 30 and 60 min after venepuncture and was concentration-dependent (60-7, 200nM). At concentrations below the TAC, U-466l9 induced primary reversible aggregation without detectable l4C-5 HT release. At TAC or higher concentrations aggregation and release proceeded as parallel events. Neither MOA production nor intracellular LDH loss could be detected in any of the tested situations. Aspirin ingestion did not modify the above pattern of platelet responses. In unstirred samples l4C - 5 HT release occurred to the same extent as in stirred platelet suspensions. Addition to citrated PRP of Na2 - EDTA did not affect either aggregation or release. It is suggested that aggregation and secretion may be independent, parallel responses of platelet activation by U-466l9 and do not require either extracellular calcium or activation of endogenous arachidonic acid metabolism. (Supported by the Italian CNR and NIH).

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.

Inhibition of platelet aggregation and arachidonic acid metabolism by B-carboline alkaloids

1993 ◽  
Vol 21 (4) ◽  
pp. 461S-461S ◽  
Author(s):  
SHEIKH A. SAEED ◽  
RUKHSANA U. SIMJEE ◽  
SAMINA FARNAZ ◽  
ANWAR H. GILANI ◽  
SALIMUZZAMAN SIDDIQUI ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Inhibition Of Platelet Aggregation

The Effects Of Chemical Alterations Of The Benzoic Acid Nucleus On Platelet Function And Prostacyclin Activity In The Arterial Wall

1981 ◽  
Author(s):  
B A Killackey ◽  
J J Killackey ◽  
R B Philp
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Benzoic Acid ◽  
Platelet Function ◽  
Platelet Rich Plasma ◽  
Atp Release ◽  
Rabbit Aorta ◽  
Arachidonic Acid Metabolism ◽  
Second Phase ◽  
Benzoic Acid Derivatives

The effects of a series of benzoic acid derivatives (ASA analogs) on prostacyclin (PGI2) synthesis by rabbit aorta rings and on human platelet function were examined to determine if antiplatelet activity could be separated from anti-PGI2 activity.Rings of rabbit aorta were incubated with or without drugs in Tris 0.05 M, pH 7.5 for 6 m at room temperature (R.T.). Supernatant was then transferred to platelet-rich plasma incubated at 37°C for 3 m. ADP was added 60 s later and aggregation was measured and compared to controls. Rings were also incubated with 14C-arachidonic acid (14C-AA) for 60 m at R.T. in Tris with or without drugs. Products were extracted and measured by radio-T.L.C. along with known standards. Platelet aggregation and release of ATP were measured using a ChronoLog Lumi aggregometer. The effects of these agents on PGI2 activity were similar to their effects on platelet aggregation. ASA however did not exhibit the marked inhibitory potency that it had on the second phase of platelet aggregation and ATP release. Changing the 2-acetoxy group of A.S.A. to a 2-acetyl or 3-propionyloxy resulted in a loss of inhibitory activity in both systems. 2-Propionyloxy substitution resulted in a similar spectrum of activity to ASA. The effects of these agents on the metabolism of 14C-AA by rabbit aorta rings generally confirmed the bioassay results although some of the agents had novel effects on blood vessel arachidonic acid metabolism.Despite potential species differences, this study demonstrates an inability to separate antiplatelet and anti-PGI2 effects with this series of benzoic acid derivatives. Further study of the effects of these agents on the metabolism of 14C-AA by rings of rabbit aorta may lead to a better understanding of PGI2 formation.

Platelet inhibition by aspirin is diminished in patients during carotid surgery: a form of transient aspirin resistance?

2004 ◽  
Vol 92 (07) ◽  
pp. 89-96 ◽  
Author(s):  
David Payne ◽  
Chris Jones ◽  
Paul Hayes ◽  
Sally Webster ◽  
A. Naylor ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Platelet Inhibition ◽  
Aspirin Resistance ◽  
Arachidonic Acid Metabolism ◽  
Significant Rise ◽  
Control Group

SummaryThe majority of patients who suffer peri-operative thromboembolic complication while undergoing vascular procedures do so despite taking aspirin. This study examined the antiplatelet effect of aspirin during surgery in patients undergoing carotid endarterectomy (CEA). Fifty patients undergoing CEA were standardised to 150 mg aspirin daily for ≥2 weeks. Platelet aggregation in response to arachidonic acid (AA) was measured in platelet rich plasma prepared from blood taken prior to, during, and at the end of surgery. Spontaneous platelet aggregation was also studied, as was the role of physiological agonists (ADP, collagen, thrombin, and epinephrine) in mediating the in vivo and in vitro responses to AA. Eighteen patients undergoing leg angioplasty, also on 150 mg aspirin, without general anaesthesia, served as a control group. In the CEA patients aggregation induced by AA (5 mM) increased significantly from 7.6 ± 5.5% pre-surgery to 50.8 ± 29.5% at the end of surgery (p <0.0001). Aggregation to AA was even greater in samples taken mid-surgery from a sub-set of patients (73.8 ± 7.2%; p = 0.0001), but fell to 45.9 ± 7.4% by the end of surgery. The increased aggregation in response to AA was not due to intra-operative release of physiological platelet agonists since addition of agents that block/neutralise the effects of ADP (apyrase; 4 µg/ml), thrombin (hirudin; 10 units/ml), or epinephrine (yohimbine; 10 µM/l) to the samples taken at the end of surgery did not block the increased aggregation.The patients undergoing angioplasty also showed a significant rise in the response to AA (5 mM), from 5.6 ± 5.5% pre-angioplasty to 32.4 ± 24.9% at the end of the procedure (p <0.0001), which fell significantly to 11.0 ± 8.1% 4 hours later. The antiplatelet activity of aspirin, mediated by blockade of platelet arachidonic acid metabolism, diminished significantly during surgery, but was partially restored by the end of the procedure without additional aspirin treatment.This rapidly inducible and transient effect may explain why some patients undergoing cardiovascular surgery remain at risk of peri-operative stroke and myocardial infarction.

scholarly journals A New Pathway for Arachidonic Acid Metabolism in Human Platelets

1977 ◽  
Author(s):  
S. Rittenhouse-Simmons ◽  
F. A. Russell ◽  
D. Deykin
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
De Novo ◽  
Platelet Rich Plasma ◽  
Gel Filtration ◽  
Kinetic Studies ◽  
Arachidonic Acid Metabolism ◽  
Biologically Active ◽  
Resting Cells ◽  
Active Metabolites

We are reporting a novel pathway of arachidonic acid metabolism in the phosphatides of thrombin-activated platelets. For kinetic studies of arachidonic acid turnover, platelet phosphatides were labeled by incubation of platelet rich plasma with (3H)-arachidonic acid for 15 min. Unincorporated isotope was removed during subsequent gel-filtration. Platelet phosphatides were resolved and quantitated following two-dimensional silica paper chromatography of chloroform/methanol extracts of incubated platelets. Plasmalogen phosphatidylethanolamine (PPE) was examined on paper chromatograms after its breakdown to lysoPPE with HgCl2. In other experiments, gel-filtered platelets were incubated with (14C)-glycerol to monitor de novo phosphatide synthesis. (3H)-Arachidonic acid was released from phosphatidylcholine and phosphatidylinositol of pre-labeled platelets exposed to thrombin and appeared increasingly in PPE in acyl linkage at glycerol-C-2. (3H)-Arachidonic acid was not found in PPE of resting cells. Maximum transfer occurred with 5 U/ml of thrombin and 15 min, of incubation, with t½ of 2½ min., and was Ca+2 dependent. The presence of aspirin, indomethacin, or eicosatetraynoic acid did not prevent the thrombin-activated transfer of (3H)-arachidonic acid to PPE. The stimulated incorporation of (3H)-arachidonic acid into PPE was not accompanied by a stimulation of (14C)-glycerol uptake into this phosphatide. We suggest that perturbation of the platelet may activate a phospholipase A2 leading to turnover of arachidonic acid in PPE, which is rich in this fatty acid. Such turnover may provide substrate for conversion by cyclo-oxygenase and lipoxydase to biologically active metabolites, and therefore, may offer a locus for regulation of prostaglandin synthesis in the human platelet.

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