The Role of Prostaglandins in the ADP-Induced Aggregation of Rabbit Platelets Shown by the Use of 15-Hydroxyprostaglandin Dehydrogenase

1978 ◽  
Vol 39 (03) ◽  
pp. 725-732 ◽  
Author(s):  
Robert B Wallis
Keyword(s):  
Platelet Rich Plasma ◽  
Shape Change ◽  
Rabbit Platelet ◽  
Direct Role ◽  
Initial Shape ◽  
Rabbit Platelets ◽  
Induced Aggregation ◽  
Aggregation Of Platelets

SummaryThe initial shape change and subsequent aggregation of platelets in citrated rabbit platelet-rich plasma caused by ADP in vitro was inhibited by 15-hydroxyprostaglandin dehydrogenase. This inhibition was NAD-dependent and was also seen when shape change and aggregation were initiated by sodium arachidonate or by collagen. The aggregation of gel-filtered rabbit platelets by thrombin was not, however, affected by removal of 15-hydroxyprostaglandins.Indomethacin was found to inhibit ADP-induced aggregation but at a concentration (250 μM) much higher than that required to inhibit collagen-induced aggregation. Moreover the platelet release reaction had not taken place 3 min after ADP stimulation. The direct role 15-hydroxyprostaglandin production in ADP-induced aggregation of rabbit platelets is proposed. The involvement of 15-hydroxyprostaglandins in platelet aggregation caused by other inducers is also discussed.

Effects of Ethanol on Pathways of Platelet Aggregation In Vitro

1988 ◽  
Vol 59 (03) ◽  
pp. 383-387 ◽  
Author(s):  
Margaret L Rand ◽  
Marian A Packham ◽  
Raelene L Kinlough-Rathbone ◽  
J Fraser Mustard
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Secondary Phase ◽  
Primary Phase ◽  
Rabbit Platelet ◽  
Membrane Phospholipids ◽  
Rabbit Platelets ◽  
Induced Aggregation

SummaryEthanol, at physiologically tolerable concentrations, did not affect the primary phase of ADP-induced aggregation of human or rabbit platelets, which is not associated with the secretion of granule contents. Potentiation by epinephrine of the primary phase of ADP-induced aggregation of rabbit platelets was also not inhibited by ethanol. However, ethanol did inhibit the secondary phase of ADP-induced aggregation which occurs with human platelets in citrated platelet-rich plasma and is dependent on the formation of thromboxane A2. Inhibition by ethanol of thromboxane production by stimulated platelets is likely due to inhibition of the mobilization of arachidonic acid from membrane phospholipids, as ethanol had little or no effect on aggregation and secretion induced by arachidonic acid or the thromboxane mimetic U46619. Rabbit platelet aggregation and secretion in response to low concentrations of collagen, thrombin, or PAF were inhibited by ethanol. Inhibition of the effects of thrombin and PAF was also observed with aspirin-treated platelets. Thus, in addition to inhibiting the mobilization of arachidonate for thromboxane formation that occurs with most agonists, ethanol can also inhibit aggregation and secretion through other effects on platelet responses.

The Effect of Molecular Iodine on Platelet Aggregation in Vitro

1974 ◽  
Vol 31 (01) ◽  
pp. 160-171 ◽  
Author(s):  
Kiyomi Kikugawa
Keyword(s):  
Platelet Aggregation ◽  
Reduced Glutathione ◽  
Platelet Rich Plasma ◽  
Molecular Iodine ◽  
Sulfhydryl Groups ◽  
Rabbit Platelet ◽  
Irreversible Aggregation ◽  
Induced Aggregation ◽  
Aggregation Of Platelets

SummaryWhen rabbit platelet-rich plasma was treated with 1-2 mM molecular iodine, marked irreversible aggregation of platelets was observed. The aggregation was characterized by inhibition by 1 mM reduced glutathione, acceleration by 0.1 mM NEM, and no interference with EDTA and adenosine which are powerful inhibitors of aggregation induced by ADP. Molecular iodine at a concentration of 0.5 mM did not induce aggregation and caused more than 60% inhibition of ADP- and collagen-induced aggregation. These findings indicated that the aggregation by molecular iodine was in quite different mechanisms from those by other aggregating agents such as ADP, and suggested that platelet aggregation by molecular iodine and ADP was greatly regulated by sulfhydryl groups.

In Vitro Effects of Ethanol on Rabbit Platelet Aggregation, Secretion of Granule Contents, and Cyclic AMP Levels in the Presence of Prostacyclin

1989 ◽  
Vol 61 (02) ◽  
pp. 254-258 ◽  
Author(s):  
Margaret L Rand ◽  
Peter L Gross ◽  
Donna M Jakowec ◽  
Marian A Packham ◽  
J Fraser Mustard
Keyword(s):  
Cyclic Amp ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Inhibitory Effects ◽  
Low Concentrations ◽  
Rabbit Platelets ◽  
High Concentrations ◽  
In Vitro Effects ◽  
Aggregation Of Platelets

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.

Effects of Bupranolol, a New β-Blocker, on Platelet Functions of Rabbit and Human in Vitro

1976 ◽  
Vol 36 (02) ◽  
pp. 376-387 ◽  
Author(s):  
Teruhiko Umetsu ◽  
Kazuko Sanai ◽  
Tadakatsu Kato
Keyword(s):  
Platelet Aggregation ◽  
Platelet Adhesion ◽  
Human Platelets ◽  
Rabbit Platelet ◽  
Rabbit Platelets ◽  
Β Blocker ◽  
Platelet Aggregates ◽  
Induced Aggregation ◽  
Platelet Functions

SummaryThe effects of bupranolol, a new β-blocker, on platelet functions were investigated in vitro in rabbits and humans as compared with propranolol, a well-known β-blocker. At first, the effect of adrenaline on ADP-induced rabbit platelet aggregation was studied because adrenaline alone induces little or no aggregation of rabbit platelets. Enhancement of ADP-induced rabbit platelet aggregation by adrenaline was confirmed, as previously reported by Sinakos and Caen (1967). In addition the degree of the enhancement was proved to be markedly affected by the concentration of ADP and to increase with decreasing concentration of ADP, although the maximum aggregation (percent) was decreased.Bupranolol and propranolol inhibited the (adrenaline-ADP-)induced aggregation of rabbit platelets, bupranolol being approximately 2.4–3.2 times as effective as propranolol. Bupranolol stimulated the disaggregation of platelet aggregates induced by a combination of adrenaline and ADP, but propranolol did not. Platelet adhesion in rabbit was also inhibited by the β-blockers and bupranolol was more active than propranolol. With human platelets, aggregation induced by adrenaline was inhibited by bupranolol about 2.8–3.3 times as effectively as propranolol.From these findings. We would suggest that bupranolol might be useful for prevention or treatment of thrombosis.

scholarly journals Loxosceles gaucho spider venom and its sphingomyelinase fraction trigger the main functions of human and rabbit platelets

2011 ◽  
Vol 30 (10) ◽  
pp. 1567-1574 ◽  
Author(s):  
Flávio L Tavares ◽  
María E Peichoto ◽  
Danieli de Morais Rangel ◽  
Kátia C Barbaro ◽  
Maria Cristina Cirillo ◽  
...  
Keyword(s):  
Platelet Adhesion ◽  
Spider Venom ◽  
Acid Generation ◽  
Rabbit Platelets ◽  
In Vitro Effects ◽  
Induced Aggregation ◽  
Dose Dependent Increase ◽  
Dose Dependent

Loxosceles venoms can promote severe local and systemic damages. We have previously reported that Loxosceles gaucho spider venom causes a severe early thrombocytopenia in rabbits. Herein, we investigated the in vitro effects of this venom and its sphingomyelinase fraction on the main functions of platelets. Whole venom and its fraction induced aggregation of both human and rabbit platelets. Aggregation was dependent of plasma component(s) but independent of venom-induced lysophosphatidic acid generation. There was no increase in the levels of lactate dehydrogenase during platelet aggregation, ruling out the possibility of platelet lysis. The increased expression of ligand-induced binding site 1 (LIBS1) induced by L. gaucho venom and its sphingomyelinase fraction, as well as of P-selectin by the whole venom, evidenced the activation state of both human and rabbit platelets. Adhesion assays showed an irregular response when platelets were exposed to the whole venom, whereas the sphingomyelinase fraction induced a dose-dependent increase in the platelet adhesion to collagen. These findings evidence that L. gaucho venom and its sphingomyelinase fraction trigger adhesion, activation, and aggregation of both human and rabbit platelets. Thus, this work justifies the use of rabbits to investigate Loxosceles venom-induced platelet disturbances, and it also supports research on the role of platelets in the pathogenesis of loxoscelism.

ETHANOL INHIBITS RABBIT PLATELET RESPONSES TO COLLAGEN IN VITRO BUT DOES NOT AFFECT RABBIT PLATELET ADHERENCE TO DE-ENDOTHELIALIZED A0RTAE IN VIVO

1987 ◽  
Author(s):  
M L Rand ◽  
H M Groves ◽  
R L Kinlough-Rathbone ◽  
M A Packham ◽  
J F Mustard
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Platelet Adherence ◽  
Induced Aggregation

Epidemiological studies indicate that moderate consumption of alcohol is associated with a reduced risk of coronary heart disease, but it is not known whether inhibition of platelet functions by ethanol is involved. We studied the effects of ethanol on rabbit platelet responses to collagen in vitro and in vivo. Addition of ethanol (4 mg/ml) to suspensions of washed platelets prelabelled with [14c]serotonin inhibited aggregation and secretion in response to low (0.4 μg/ml) concentrations of acid soluble collagen (14% secretion without ethanol, 3% secretion with ethanol). With a higher concentration of collagen (1.25 μg/ml), 4 mg/ml ethanol had no inhibitory effect. The inhibitory effect of ethanol on collagen-induced aggregation was also observed in citrated platelet-rich plasma (c-PRP) to which ethanol was added in vitro and in c-PRP from rabbits given ethanol acutely by gavage (3.5 g/kg) 30 min before blood sampling. The accumulation of [51cr]-labeled platelets on the subendothelium of rabbit aortae de-endothelialized with balloon catheters was measured in vivo in rabbits given ethanol (blood ethanol concentration at time of vessel wall injury: 4.1 ± 0.2 mg/ml, mean ± S.E., n=6). Ten min after de-endothelialization, there was no difference between the number of platelets adherent per square mm of injured aorta of control rabbits (39,400 ± 2,600, mean ± S.E., n=6) and intoxicated rabbits (36,800 ± 3,700, mean ± S.E., n=6). Thus, although ethanol inhibits platelet aggregation and secretion in response to collagen in vitro and ex vivo, it does not alter platelet adherence to the subendothelium, including its constituent collagen, in vivo. Therefore, it is unlikely that ethanol exerts its beneficial effects against coronary heart disease by altering the initial adherence of platelets to injured vessel walls.

scholarly journals Structurally Diverse Metal Coordination Compounds, Bearing Imidodiphosphinate and Diphosphinoamine Ligands, as Potential Inhibitors of the Platelet Activating Factor

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Alexandros B. Tsoupras ◽  
Maria Roulia ◽  
Eleftherios Ferentinos ◽  
Ioannis Stamatopoulos ◽  
Constantinos A. Demopoulos ◽  
...  
Keyword(s):  
Platelet Rich Plasma ◽  
Platelet Activating Factor ◽  
Three Dimensional ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Square Planar ◽  
Rabbit Platelets ◽  
Potential Inhibitors ◽  
Induced Aggregation ◽  
Related Pathway

Metal complexes bearing dichalcogenated imidodiphosphinate[R2P(E)NP(E)R2′]-ligands (E = O, S, Se, Te), which act as (E,E) chelates, exhibit a remarkable variety of three-dimensional structures. A series of such complexes, namely, square-planar[Cu{(OPPh2)(OPPh2)N-O,O}2], tetrahedral[Zn{(EPPh2)(EPPh2)N-E,E}2], E = O, S, and octahedral[Ga{(OPPh2)(OPPh2)N-O,O}3], were tested as potential inhibitors of either the platelet activating factor (PAF)- or thrombin-induced aggregation in both washed rabbit platelets and rabbit platelet rich plasma. For comparison, square-planar[Ni{(Ph2P)2N-S-CHMePh-P,P}X2], X = Cl, Br, the corresponding metal salts of all complexes and the(OPPh2)(OPPh2)NHligand were also investigated.Ga(O,O)3showed the highest anti-PAF activity but did not inhibit the thrombin-related pathway, whereasZn(S,S)2, with also a significant PAF inhibitory effect, exhibited the highest thrombin-related inhibition.Zn(O,O)2andCu(O,O)2inhibited moderately both PAF and thrombin, being more effective towards PAF. This work shows that the PAF-inhibitory action depends on the structure of the complexes studied, with the bulkierGa(O,O)3being the most efficient and selective inhibitor.

Acetyisalicylic Acid (ASA) does not Prolong Bleeding Time in Rats

1975 ◽  
Author(s):  
L. Stella ◽  
M. B. Donati ◽  
G. de Gaetano
Keyword(s):  
Research Council ◽  
Bleeding Time ◽  
Satisfactory Explanation ◽  
Lysine Acetylsalicylate ◽  
Induced Aggregation ◽  
Aggregation Of Platelets

We have recently suggested (Thrombos. Diathes. haemorrh., 32, 242, 1974; Thrombos. Res., 1975, in press) that the role of platelets in the primary haeomostasis of rats may be questioned. Further evidence to this hypothesis is given by this study. Indeed, we have observed that ASA does not prolong the bleeding time in rats, whereas it inhibits in vitro collagen- or Thrombofax-induced aggregation of platelets obtained from the same animals after administration of the drug. Conscious Charles River rats, weighing 350 g., were used. Aspirin (Bayer) or lysine-acetylsalicylate (Flectadol, Maggioni) were given either per os or intrapertioneally at a dose of 200 mg/kg b.w. The effect on the bleeding time was measured 1 hour after the administration of the drug by 2 different techniques: either transecting the tip of the tails of paired animals or making 2 incisions on the tail of the same animal by an automatic, standardized template-like device (kindly provided by Prof. C. Praga, Milano). Preliminary experiments in control animals had shown no difference between the first and the second incision. The results are reported in the table.As can be seen, ASA not only did not prolong bleeding time, but markedly shortened it. The latter result was unexpected and we have no satisfactory explanation for ist.(Supported by Grant N. 73.00400.04 of the Italian Research Council (C. N. R.).)

ADP-Induced Refractory State of Platelets in Vitro

1975 ◽  
Author(s):  
S. Holme ◽  
H. Holmsen ◽  
J. J. Sixma
Keyword(s):  
Dose Response ◽  
Platelet Rich Plasma ◽  
Shape Change ◽  
Response Curves ◽  
Aggregation Response ◽  
Maximal Height ◽  
Refractory State ◽  
Change Response ◽  
Induced Aggregation

ADP-induced aggregation was determined at various times of pre-incubation with ADP in unstirred platelet rich plasma to which adenosine deaminase was added. In the early stages of incubation the shape change response was absent, the aggregation response was poor and not reversible. As incubation proceeded, these three parameters returned towards normal while there was still ADP in the system. Log dose response (rate of aggregation) curves for the platelets incubated with 1 μM of ADP had shifted to higher concentrations of ADP and there was a small decrease in the maximal height of the curves. Gelfiltered platelets in calcium-free Tyrode solution were incubated with 1 μM of ADP at 37° C. Log dose response curves obtained at different times of incubation showed a greater shift to higher ADP concentrations than those obtained with platelets in plasma. There was also a pronounced decrease in the maximal height of the curves. These two observations became more apparent as incubation proceeded. Addition of apyrase (0.1 mg/ml) at various times of incubation prevented the progessive impairment of the aggregation response and this even slowly increased towards that of the control. The time of incubation with ADP before addition of apyrase did not have any influence on the ability of the platelets to recover their aggregability towards ADP.

LY53857, a 5HT2 Receptor Antagonist, Delays Occlusion and Inhibits Platelet Aggregation in a Rabbit Model of Carotid Artery Occlusion

1991 ◽  
Vol 66 (03) ◽  
pp. 355-360 ◽  
Author(s):  
Harve C Wilson ◽  
William Coffman ◽  
Anne L Killam ◽  
Marlene L Cohen
Keyword(s):  
Electrical Stimulation ◽  
Platelet Aggregation ◽  
Carotid Artery ◽  
Receptor Antagonist ◽  
Artery Occlusion ◽  
Carotid Artery Occlusion ◽  
Rabbit Platelet ◽  
Rabbit Platelets ◽  
5Ht2 Receptor

SummaryThe present study was designed to evaluate the effectiveness of the ergoline 5HT2 receptor antagonist, LY53857 in a rabbit model of vascular arterial occlusion. LY53857 (1 and 10 εM) inhibited serotonin amplified platelet aggregation responses to threshold concentrations of ADP in rabbit platelets in vitro. LY53857 (1 εM) not only inhibited the serotonin component of rabbit platelet aggregation, but also inhibited in vitro aggregation induced by ADP (48.7 ± 16.7% inhibition), collagen (76.1 ± 15.9% inhibition) and U46619 (65.2 ± 12.3% inhibition). The effectiveness of this ergoline 5HT2 receptor antagonist in blocking aggregation to ADP, collagen and U46619 may be related to its ability to inhibit a serotonin component of platelet aggregation since rabbit platelets possess high concentrations of serotonin that may be released during aggregation produced by other agents. Based on the effectiveness of LY53857 to inhibit rabbit platelet aggregation, we explored the ability of LY53857 to extend the time to carotid artery occlusion in rabbits following electrical stimulation of the artery. Reproducible carotid artery occlusion was induced in rabbits by moderate stenosis coupled to arterial cross clamping, followed by electrical stimulation. With this procedure, occlusion occurred at 47.0 ± 7 min (n = 30) after initiation of the electrical stimulation. Animals pretreated with LY53857 (50 to 500 εg/kg i.v.) showed a delay in the time to carotid artery occlusion (at 100 εg/kg i.v. occlusion time extended to 164 ± 16 min). Furthermore, ex vivo platelet aggregation from animals treated with LY53857 (300 εg/kg i.v.) resulted in 40.5% inhibition of platelet aggregation in response to the combination of ADP (1 εM) and serotonin (1 εM). These studies document the ability to obtain reproducible arterial occlusion in the rabbit and showed that intravenously administered LY53857 prolonged the time to carotid artery occlusion. Prolongation of carotid artery occlusion time was accompanied by inhibition of serotonin-amplified ADP-induced aggregation in rabbit platelets, an effect observed both in vitro and ex vivo. Thus, the rabbit is a useful model for studying the effectiveness of 5HT2 receptor antagonists in prolonging vascular occlusion induced by insult of the carotid artery.

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