scholarly journals Search for Naturally Occurring Substances to Prevent the Complications of Diabetes. II. Inhibitory Effect of Coumarin and Flavonoid Derivatives on Bovine Lens Aldose Reductase and Rabbit Platelet Aggregation.

1995 ◽  
Vol 43 (8) ◽  
pp. 1385-1387 ◽  
Author(s):  
Yoshihito OKADA ◽  
Noriaki MIYAUCHI ◽  
Katsuhisa SUZUKI ◽  
Toshimitsu KOBAYASHI ◽  
Chiaki TSUTSUI ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Aldose Reductase ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Complications Of Diabetes ◽  
Bovine Lens ◽  
Naturally Occurring

Inhibitory effect of pyridyloxy- or phenoxylphenoxyalkanate derivatives on rat lens aldose reductase and rat platelet aggregation

2004 ◽  
Vol 56 (7) ◽  
pp. 941-945 ◽  
Author(s):  
Soon Sung Lim ◽  
Kuk Hyun Shin ◽  
Sang Hoon Jung ◽  
Kye Jung Shin ◽  
Dong Chan Kim ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Aldose Reductase ◽  
Inhibitory Effect ◽  
Rat Lens Aldose Reductase

Inhibitory Effect Of Exogenous Arachidonic Acid Or Linoleic Acid On Rabbit Platelet Aggregation And Release Reaction

1981 ◽  
Author(s):  
M Cattaneo ◽  
R L Kinlough-Rathbone ◽  
J F Mustard
Keyword(s):  
Arachidonic Acid ◽  
Linoleic Acid ◽  
Platelet Aggregation ◽  
Cell Membrane ◽  
Platelet Function ◽  
Unsaturated Fatty Acids ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Lipoxygenase Pathway ◽  
High Concentrations

In contrast to other release-inducing agents (e.g. thrombin) arachidonic acid (AA) releases only 40-50% of amine storage granule contents and although low concentrations induce aggregation, high concentrations do not. Several theories have been proposed to explain these observations: 1) AA or its products inactivates the cyclo-oxygenase; 2) the products of AA increase platelet cAMP; 3) lipoxygenase products are inhibitory; 4) unsaturated fatty acids (UFA) perturb the cell membrane. Using washed rabbit platelets we examined the effect of AA on platelet function. In these experiments aspirin-treated platelets (ASA 5.5 mM) were exposed to AA (230 μM) for 15 min. and then to PGEj (10 μM) for 30 min. The platelets were then resuspended. These platelets did not aggregate to ADP (9 μM) and their response to thrombin (0.02-0.05 U/ml) was impaired in contrast to control, ASA-treated platelets not exposed to AA. Non-ASA-treated platelets exposed to AA (230 μM), deaggre- gated with PGE1, and then resuspended also did not aggregate in response to ADP (9 μM) collagen, AA (230 μM) or thrombin (0.02-0.05 U/ml). When platelets pretreated with ASA and AA were mixed 1:1 with normal platelets and the mixture stimulated with AA (230 μM), the AA-treated platelets did not release their granule contents whereas the normal platelets did. These results do not support the hypothesis- that the inhibitory effect of AA on platelet aggregation and release is primarily due to inhibition of cyclo-oxygenase or an increase in cAMP caused by AA products. It seems unlikely that inhibition by AA can be due to products of the lipoxygenase pathway, because the effect persists when the platelets are washed and resuspended. Similar results were obtained by incubating platelets with linoleic acid (230 μM). This evidence is compatible with the hypothesis that UFA can inhibit platelet function by perturbing the cell membrane. This effect may be related to changes in receptor availability.

scholarly journals The inhibitory effects of exogenous arachidonic acid on rabbit platelet aggregation and the release reaction

Blood ◽  
1982 ◽  
Vol 60 (5) ◽  
pp. 1179-1187
Author(s):  
M Cattaneo ◽  
RL Kinlough-Rathbone ◽  
DW Perry ◽  
A Chahil ◽  
JD Vickers ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Cyclic Amp ◽  
Thromboxane A2 ◽  
Nordihydroguaiaretic Acid ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
General Effect ◽  
Lipoxygenase Pathway ◽  
Free Arachidonic Acid

Although arachidonic acid causes rabbit platelet aggregation and the release of granule contents in suspensions of washed platelets when used in concentrations of approximately 50–300 microM, higher concentrations (500 microM) cause neither aggregation nor release. Suspensions of platelets from rabbits wee exposed to arachidonic acid (250 microM) for 15 min, allowed to recover in the presence of PGE1 for 30 min, washed, and resuspended; in some experiments, the platelets were treated with aspirin before being exposed to arachidonic acid. Aggregation of platelets pretreated with arachidonic acid was inhibited in response to ADP; this effect was greater with the non-aspirin- treated platelets and persisted for at least 4 hr after resuspension. The association of 125I-fibrinogen with the platelets as a result of ADP stimulation was also inhibited. Aggregation and release of granule contents in response to collagen and low concentrations of thrombin was inhibited, but the inhibition could be overcome by higher concentrations. Thrombin induced further release of granule contents from platelets exposed to arachidonic acid without pretreatment with aspirin. Platelets that had been exposed to arachidonic acid, either with or without pretreatment with aspirin, did not aggregate or undergo further release upon stimulation with arachidonic acid after they were washed and resuspended. Inhibition of the lipoxygenase pathway with eicosatetraynoic acid (ETYA) or nordihydroguaiaretic acid (NDGA) did not affect the inhibition caused by arachidonic acid, so it is unlikely that a product of this pathway is responsible for the inhibition. Mixing experiments indicated that the pretreated platelets did not form a thromboxane-A2-like activity, and that they were unresponsive to aggregation and release induced by products formed from arachidonic acid. Experiments with 3H-arachidonic acid showed that after 45 min of incubation with platelets, only 1.1% of the 3H-arachidonic acid remained as free arachidonic acid in the platelets. Although cyclic-AMP was slightly increased 1 min after the addition of arachidonic acid, the cyclic-AMP concentration was the same as that of control platelets after the platelets were washed and resuspended, indicating that increased cyclic-AMP is not likely to be responsible for the persistent inhibitory effect. Thus, the inhibitory effect of pretreatment with arachidonic acid is a general effect on responses to a variety of aggregating agents that act through different mechanisms, and the inhibition is not related to thromboxane-A2 formation. The possibility of membrane perturbation resulting in the unavailability of receptors may explain the persistent inhibitory effect, but the responsible reactions have not been identified.

Competitive Inhibition by Lithium and Hydrogen lons of the Effect of Calcium on the Aggregation of Rabbit Platelets

1976 ◽  
Vol 36 (02) ◽  
pp. 343-359 ◽  
Author(s):  
Esther R. Anderson ◽  
J. G Foulks
Keyword(s):  
Platelet Aggregation ◽  
Competitive Inhibition ◽  
Platelet Rich Plasma ◽  
Shape Change ◽  
Inhibitory Effect ◽  
Ion Concentration ◽  
Rabbit Platelet ◽  
Kinetic Evaluation ◽  
Hydrogen Ion Concentration ◽  
Competitive Antagonism

SummaryADP-induced platelet aggregation and shape change were monitored optically in citrated rabbit platelet-rich plasma (PRP) diluted with isotonic salt solutions. Lithium (Li) produced a concentration-dependent reduction in the rate of platelet aggregation but had no discernible effect on the shape change which precedes aggregation. When PRP was pre-incubated with Li, the inhibitory effect of the ion was independent of the duration and temperature of the treatment. The inhibitory effect of Li also was observed in heparinized PRP or when 5-HT was used as the aggregation-inducing agent. When Li was combined with aggregation inhibitors which enhance platelet cyclic AMP content either by activating adenylate cyclase or by inhibiting phosphodiesterase, only additive effects were observed. The inhibitory effect of Li was opposed by added calcium. Kinetic evaluation of the interaction between Li and Ca indicated that their antagonism was competitive. Added calcium also displayed competitive antagonism toward the aggregation inhibiting effect of increased hydrogen ion concentration in the pH range between 6 and 8.

scholarly journals Inhibitory Effect of Ethanol Extract of Piper longum L. on Rabbit Platelet Aggregation through Antagonizing Thromboxane A2 Receptor

2007 ◽  
Vol 30 (7) ◽  
pp. 1221-1225 ◽  
Author(s):  
Masaya Iwashita ◽  
Masaki Saito ◽  
Yasunaga Yamaguchi ◽  
Ryoji Takagaki ◽  
Norimichi Nakahata
Keyword(s):  
Platelet Aggregation ◽  
Thromboxane A2 ◽  
Ethanol Extract ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Piper Longum ◽  
Thromboxane A2 Receptor

scholarly journals The inhibitory effects of exogenous arachidonic acid on rabbit platelet aggregation and the release reaction

Blood ◽  
1982 ◽  
Vol 60 (5) ◽  
pp. 1179-1187 ◽  
Author(s):  
M Cattaneo ◽  
RL Kinlough-Rathbone ◽  
DW Perry ◽  
A Chahil ◽  
JD Vickers ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Cyclic Amp ◽  
Thromboxane A2 ◽  
Nordihydroguaiaretic Acid ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
General Effect ◽  
Lipoxygenase Pathway ◽  
Free Arachidonic Acid

Abstract Although arachidonic acid causes rabbit platelet aggregation and the release of granule contents in suspensions of washed platelets when used in concentrations of approximately 50–300 microM, higher concentrations (500 microM) cause neither aggregation nor release. Suspensions of platelets from rabbits wee exposed to arachidonic acid (250 microM) for 15 min, allowed to recover in the presence of PGE1 for 30 min, washed, and resuspended; in some experiments, the platelets were treated with aspirin before being exposed to arachidonic acid. Aggregation of platelets pretreated with arachidonic acid was inhibited in response to ADP; this effect was greater with the non-aspirin- treated platelets and persisted for at least 4 hr after resuspension. The association of 125I-fibrinogen with the platelets as a result of ADP stimulation was also inhibited. Aggregation and release of granule contents in response to collagen and low concentrations of thrombin was inhibited, but the inhibition could be overcome by higher concentrations. Thrombin induced further release of granule contents from platelets exposed to arachidonic acid without pretreatment with aspirin. Platelets that had been exposed to arachidonic acid, either with or without pretreatment with aspirin, did not aggregate or undergo further release upon stimulation with arachidonic acid after they were washed and resuspended. Inhibition of the lipoxygenase pathway with eicosatetraynoic acid (ETYA) or nordihydroguaiaretic acid (NDGA) did not affect the inhibition caused by arachidonic acid, so it is unlikely that a product of this pathway is responsible for the inhibition. Mixing experiments indicated that the pretreated platelets did not form a thromboxane-A2-like activity, and that they were unresponsive to aggregation and release induced by products formed from arachidonic acid. Experiments with 3H-arachidonic acid showed that after 45 min of incubation with platelets, only 1.1% of the 3H-arachidonic acid remained as free arachidonic acid in the platelets. Although cyclic-AMP was slightly increased 1 min after the addition of arachidonic acid, the cyclic-AMP concentration was the same as that of control platelets after the platelets were washed and resuspended, indicating that increased cyclic-AMP is not likely to be responsible for the persistent inhibitory effect. Thus, the inhibitory effect of pretreatment with arachidonic acid is a general effect on responses to a variety of aggregating agents that act through different mechanisms, and the inhibition is not related to thromboxane-A2 formation. The possibility of membrane perturbation resulting in the unavailability of receptors may explain the persistent inhibitory effect, but the responsible reactions have not been identified.

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