Unsaturated fatty acids inhibit ADP- arachidonate-induced platelet aggregation without affecting thromboxane synthesis

1986 ◽  
Vol 64 (9) ◽  
pp. 906-913 ◽  
Author(s):  
Ella Dratewka-Kos ◽  
D. O. Tinker ◽  
Brigitte Kindl
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Platelet Aggregation ◽  
Unsaturated Fatty Acids ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Low Concentrations ◽  
Fatty Acid Inhibition ◽  
Induced Aggregation ◽  
Protein Free Medium

The inhibitory effects of three cis-unsaturated C18 fatty acids (oleic, linoleic, and linolenic acids, sodium salts) on ADP- and sodium-arachidonate-induced aggregation of washed rabbit platelets were investigated. When the platelets were suspended in protein-free medium containing dextran, it was found that these fatty acids at very low concentrations (2–45 μM) were potent inhibitors of platelet responsiveness and the inhibitory effect occurred within seconds. The inhibition of ADP-induced aggregation was not affected by abolishing the activity of platelet cyclooxygenase using aspirin. Human serum albumin relieved the inhibition caused by fatty acids for both ADP- and arachidonate-induced aggregation. The inhibitory effect of fatty acids does not seem to be due to decreased thromboxane formation (except possibly in the case of linolenate), and the relief of fatty acid inhibition by albumin does not potentiate thromboxane B2 formation from exogenous arachidonate. It is suggested that the inhibitory effect of polyunsaturated fatty acids on platelet aggregation is specific and not related to a general surfactant effect, since inhibition occurs far below the critical micelle concentration of fatty acid soaps.

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.

Platelet Aggregation in Finnish Men and Its Relation to Fatty Acids in Platelets, Plasma and Adipose Tissue

1985 ◽  
Vol 54 (03) ◽  
pp. 563-569 ◽  
Author(s):  
M K Salo ◽  
E Vartiainen ◽  
P Puska ◽  
T Nikkari
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Platelet Aggregation ◽  
Acid Composition ◽  
Saturated Fatty Acids ◽  
Free Living ◽  
Ω3 Fatty Acids ◽  
Induced Aggregation

SummaryPlatelet aggregation and its relation to fatty acid composition of platelets, plasma and adipose tissue was determined in 196 randomly selected, free-living, 40-49-year-old men in two regions of Finland (east and southwest) with a nearly twofold difference in the IHD rate.There were no significant east-southwest differences in platelet aggregation induced with ADP, thrombin or epinephrine. ADP-induced platelet secondary aggregation showed significant negative associations with all C20-C22 ω3-fatty acids in platelets (r = -0.26 - -0.40) and with the platelet 20: 5ω3/20: 4ω 6 and ω3/ ω6 ratios, but significant positive correlations with the contents of 18:2 in adipose tissue (r = 0.20) and plasma triglycerides (TG) (r = 0.29). Epinephrine-induced aggregation correlated negatively with 20: 5ω 3 in plasma cholesteryl esters (CE) (r = -0.23) and TG (r = -0.29), and positively with the total percentage of saturated fatty acids in platelets (r = 0.33), but had no significant correlations with any of the ω6-fatty acids. Thrombin-induced aggregation correlated negatively with the ω3/6ω ratio in adipose tissue (r = -0.25) and the 20: 3ω6/20: 4ω 6 ratio in plasma CE (r = -0.27) and free fatty acids (FFA) (r = -0.23), and positively with adipose tissue 18:2 (r = 0.23) and 20:4ω6 (r = 0.22) in plasma phospholipids (PL).The percentages of prostanoid precursors in platelet lipids, i. e. 20: 3ω 6, 20: 4ω 6 and 20 :5ω 3, correlated best with the same fatty acids in plasma CE (r = 0.32 - 0.77) and PL (r = 0.28 - 0.74). Platelet 20: 5ω 3 had highly significant negative correlations with the percentage of 18:2 in adipose tissue and all plasma lipid fractions (r = -0.35 - -0.44).These results suggest that, among a free-living population, relatively small changes in the fatty acid composition of plasma and platelets may be reflected in significant differences in platelet aggregation, and that an increase in linoleate-rich vegetable fat in the diet may not affect platelet function favourably unless it is accompanied by an adequate supply of ω3 fatty acids.

STUDIES OF FATTY ACID OXIDATION: 4. THE EFFECTS OF FATTY ACIDS ON THE OXIDATION OF OTHER METABOLITES

1956 ◽  
Vol 34 (6) ◽  
pp. 1211-1225 ◽  
Author(s):  
P. G. Scholefield
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Respiratory Activity ◽  
Tricarboxylic Acid Cycle ◽  
Rat Kidney ◽  
Brain Mitochondria ◽  
Acid Oxidation ◽  
Inhibitory Effects ◽  
Kidney Mitochondria ◽  
Low Concentrations

Fatty acids inhibit the oxidation of pyruvate by rat-kidney mitochondria but the extent of inhibition depends upon the nature and amount of agent added to stimulate the oxidation. The longer chain fatty acids are more effective inhibitors and, in general, the even-numbered fatty acids show greater inhibitory effects than the adjacent odd-numbered fatty acids. Under conditions where 2, 4-dinitrophenol (DNOP) and the fatty acids separately have little effect on the respiratory activity of rat-kidney mitochondria with pyruvate as substrate, the addition of both fatty acid and DNOP results in an extensive inhibition. At low concentrations the fatty acids are oxidized by rat-kidney mitochondria but at concentrations of 10−3 M and higher they inhibit their own oxidation, the oxidation of pyruvate, and those of the acids of the tricarboxylic acid cycle. The oxidation of pyruvate by rat-brain mitochondria is insensitive to decanoate but both the fumarate- and DNOP-stimulated oxidations of pyruvate are sensitive to the presence of decanoate. In contrast, Nembutal inhibits both the oxidation of pyruvate alone and the fumarate-stimulated oxidation of pyruvate. Possible mechanisms for the observed inhibitory effects of fatty acids are discussed.

The Effect of Fatty Acids upon Tumor Cell Respiration and Transplantability

1963 ◽  
Vol 9 (5) ◽  
pp. 530-543 ◽  
Author(s):  
Bernard J Katchman ◽  
Robert E Zipf ◽  
James P F Murphy
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Tumor Cells ◽  
Chemical Structure ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Leukemic Cells ◽  
Endogenous Respiration ◽  
Low Concentrations

Abstract The kinetic effect of palmitate, stearate, oleate, linoleate, and linolenate upon in vitro endogenous respiration of rat chloromyeloid leukemic cells has been investigated. Inhibition of respiration has been correlated with the ability of fatty acids to cause decreased cell viability and cell count; in the bioassay of fatty acid-treated tumor inocula, the increase in animal life span is correlated to the degree of dilution of the inocula due to cell lysis. The degree of lysis is dependent upon the chemical structure of the fatty acid, concentration, and duration of contact; unsaturated fatty acids are more effective than saturated fatty acids. Tumor cells, when incubated at low concentrations of fatty acids, show stimulation of O2 uptake; however, in the bioassay these fatty acid-treated inocula showed no loss in tumor activity. The nature of the physiochemical interaction between fatty acids and tumor cells is discussed.

scholarly journals Fatty acid modulation and polyamine block of GluK2 kainate receptors analyzed by scanning mutagenesis

2010 ◽  
Vol 136 (3) ◽  
pp. 339-352 ◽  
Author(s):  
Timothy J. Wilding ◽  
Kevin Chen ◽  
James E. Huettner
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Unsaturated Fatty Acids ◽  
Kainate Receptors ◽  
Transmembrane Helices ◽  
Ionic Selectivity ◽  
Chloride Permeability ◽  
Central Cavity ◽  
Whole Cell ◽  
Fatty Acid Inhibition

RNA editing of kainate receptor subunits at the Q/R site determines their susceptibility to inhibition by cis-unsaturated fatty acids as well as block by cytoplasmic polyamines. Channels comprised of unedited (Q) subunits are strongly blocked by polyamines, but insensitive to fatty acids, such as arachidonic acid (AA) and docosahexaenoic acid (DHA), whereas homomeric edited (R) channels resist polyamine block but are inhibited by AA and DHA. In the present study, we have analyzed fatty acid modulation of whole-cell currents mediated by homomeric recombinant GluK2 (formerly GluR6) channels with individual residues in the pore-loop, M1 and M3 transmembrane helices replaced by scanning mutagenesis. Our results define three abutting surfaces along the M1, M2, and M3 helices where gain-of-function substitutions render GluK2(Q) channels susceptible to fatty acid inhibition. In addition, we identify four locations in the M3 helix (F611, L614, S618, and T621) at the level of the central cavity where Arg substitution increases relative permeability to chloride and eliminates polyamine block. Remarkably, for two of these positions, L614R and S618R, exposure to fatty acids reduces the apparent chloride permeability and potentiates whole-cell currents ∼5 and 2.5-fold, respectively. Together, our results suggest that AA and DHA alter the orientation of M3 in the open state, depending on contacts at the interface between M1, M2, and M3. Moreover, our results demonstrate the importance of side chains within the central cavity in determining ionic selectivity and block by cytoplasmic polyamines despite the inverted orientation of GluK2 as compared with potassium channels and other pore-loop family members.

A POSSIBLE MECHANISM FOR FATTY ACID INHIBITION OF CHOLESTEROL SYNTHESIS

1957 ◽  
Vol 35 (1) ◽  
pp. 645-653
Author(s):  
J. D. Wood ◽  
B. B. Migicovsky
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cholesterol Synthesis ◽  
Unsaturated Fatty Acids ◽  
Cholesterol Biosynthesis ◽  
Saturated Fatty Acids ◽  
Liver Homogenate ◽  
Acid Inhibition ◽  
Acetyl Coa ◽  
Fatty Acid Inhibition

Further investigations have been carried out on the fatty acid inhibition of cholesterol biosynthesis in rat liver homogenates. A correlation appears to exist between cholesterol inhibition and the elongation of the carbon chain of saturated fatty acids containing an even number of carbon atoms. Neither saturated nor unsaturated fatty acids interfere with the formation of acetyl CoA by liver homogenate. The stage where acetoacetate is formed from acetyl CoA is suggested as a possible site for inhibition of cholesterol synthesis by fatty acids.

Discrimination Between Prostglandin-Dependent And-Independent Functions Of Essential Fatty Acids In Arterial Throm- Bogenesis

1981 ◽  
Author(s):  
U M T Houtsmuller ◽  
G Hornstra ◽  
E Haddeman
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Platelet Aggregation ◽  
Arterial Thrombosis ◽  
Thrombus Formation ◽  
Arterial Thrombus ◽  
Induced Aggregation

Arterial thrombus formation is reduced in essential fatty acid (EFA) deficiency. This goes together with an enhanced thrombin induced aggregation of platelets in vitro,whereas collagen-induced aggregation is definitely suppressed. A small amount of linoleic acid (18:2 (n-6)) is able to cure EFA-deficiency and to normalize arterial thrombogenesis. This latter effect may be due to either the structural function of this EFA or to its function as the ultimate dietary precursor of prostaglandins (PG). Columbinic acid, a stereo-isomer of γ-linolenic acid (18:3 (n-6)) was recently shown to possess all the structural functions of EFA, but not the PG-dependent ones. This fatty acid therefore presents a suitable tool to investigate the PG-dependence of arterial thrombogenesis and its underlying processes. We therefore compared the effect of small amounts of linoleic and columbinic acid (both as methylesters) on the water vapour release in vivo (which is a sensitive parameter for a non-PG dependent function of polyenoic fatty acids), arterial thrombosis tendency (time needed for the thrombotic obstruction of an aorta prosthesis) and platelet aggregation in vitro (aggregometry) induced by collagen and thrombin. In contrast to linoleic acid, columbinic acid did not normalize arterial thrombosis tendency and collagen induced platelet aggregation. Columbinic acid was equally effective as linoleic acid in the normalization of the water vapour release in vivo and of the thrombin-induced aggregation. We conclude that arterial thrombus formation and collagen- induced aggregation greatly depend on prostanoid formation, whereas thrombin-induced aggregation does not. The structural role of polyenoic fatty acids in thrombin-induced aggregation may provide a tool in the elucidation of factors determining the thrombin-sensitivity of blood platelets.

Inhibitory effects of antibiotics on platelet aggregation in vitro

1997 ◽  
Vol 16 (11) ◽  
pp. 662-666 ◽  
Author(s):  
Hiroko Kariyazono ◽  
Kazuo Nakamura ◽  
Terutoshi Shinkawa ◽  
Yukinori Moriyama ◽  
Hitoshi Toyohira ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Blood Concentration ◽  
Chemical Structure ◽  
Inhibitory Action ◽  
Adenosine Diphosphate ◽  
Inhibitory Effect ◽  
Carboxyl Group ◽  
Inhibitory Effects ◽  
Induced Aggregation

1 We evaluated in vitro inhibitory effects of six types of antibiotic, aztreonam (AZT), cefamandole (CMD), cefmetazole (CMZ), cefotiam (CTM), flomoxef (FMOX) and latamoxef (LMOX), on platelet aggregation, using healthy volunteers' blood. Four types-FMOX, LMOX, CTM and CMD-inhibited, in concentration of 2500 ?g/ml, the secondary aggregation induced by 3.0 ?M adenosine diphosphate (ADP), and also inhibited the aggregation induced by 0.5 ?g/ml collagen. AZT in the same concentration, did not inhibit the aggregation induced by collagen, and it inhibited only ADP induced aggregation. CMZ, in the same concentration, inhibited neither of the two aggregations. 2 The inhibitory effects of the antibiotics on collagen- induced aggregation were dependent on the concen tration of respective antibiotics. When classified by the strength of inhibitory action, LMOX and FMOX were strong, followed by CTM and CMD. The action of AZT and CMZ was weak. In particular, LMOX showed a 32% inhibitory effect at concentration of 50 ?g/ml, a level near the blood concentration obtained with clinical usual dose. 3 No relationship was observed between inhibitory effects of antibiotics on ADP- or collagen-induced aggregation and the presence or absence of carboxyl group and/or N-methyltetrazolethiol group in the chemical structure.

scholarly journals Effects of thia-substituted fatty acids on mitochondrial and peroxisomal β-oxidation. Studies in vivo and in vitro

1990 ◽  
Vol 270 (1) ◽  
pp. 167-173 ◽  
Author(s):  
R Hovik ◽  
H Osmundsen ◽  
R Berge ◽  
A Aarsland ◽  
S Bergseth ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Competitive Inhibition ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Duration Of Treatment ◽  
Acyl Coa Oxidase ◽  
Dose Dependent

1. The effects of 3-, 4- and 5-thia-substituted fatty acids on mitochondrial and peroxisomal β-oxidation have been investigated. When the sulphur atom is in the 4-position, the resulting thia-substituted fatty acid becomes a powerful inhibitor of β-oxidation. 2. This inhibition cannot be explained in terms of simple competitive inhibition, a phenomenon which characterizes the inhibitory effects of 3- and 5-thia-substituted fatty acids. The inhibitory sites for 4-thia-substituted fatty acids are most likely to be the acyl-CoA dehydrogenase in mitochondria and the acyl-CoA oxidase in peroxisomes. 3. The inhibitory effect of 4-thia-substituted fatty acids is expressed both in vitro and in vivo. The effect in vitro is instantaneous, with up to 95% inhibition of palmitoylcarnitine oxidation. The effect in vivo, in contrast, is dose-dependent and increases with duration of treatment. 4. Pretreatment of rats with a 3-thia-substituted fatty acid rendered mitochondrial β-oxidation less sensitive to inhibition by 4-thia-substituted fatty acids.

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