RELEASE OF ENDOTHELIUM DERIVED RELAXING FACTOR (EDRF), PROSTACYCLIN (PGI2) AND ANTI-PLATELET ACTIVITY BY RABBIT AORTIC ENDOTHELIUM

1987 ◽  
Author(s):  
H Bult ◽  
F Jordaens ◽  
A G Herman ◽  
C Van Hove ◽  
T J Verbeuren
Keyword(s):  
Platelet Reactivity ◽  
Platelet Rich Plasma ◽  
Rabbit Aorta ◽  
Platelet Activity ◽  
Aortic Endothelium ◽  
Specific Radioimmunoassay ◽  
Arterial Smooth Muscle Cells ◽  
Set Up ◽  
Induced Aggregation ◽  
Dose Dependent

Endothelium may release EDRF and PGI2; the former causes relaxation of arterial smooth muscle cells, whereas PGI2 suppresses phagocyte and platelet activation and may relax some arteries. The aim of the present experiments was to investigate whether EDRF from rabbit aorta affects platelet reactivity. To this end the isolated thoracic aorta was perfused with a Krebs' solution (3 ml/min), andthe perfusate was continuously super fused over a de-endothe-lialized ring of the abdominal aorta, contracted withnoradrenaline in the presence of atropine, to monitor EDRF. Aliquots (200 μl) ofeffluent were also added to 200 (il prewarmedautologous citrate platelet rich plasma, which was immediately stimulated with ADP or U46619, a thromboxane (TX) A2 mimetic. Both agonists induce aggregation independently of TXA2 formation. Finally, the PGI2 content of the effluent was assessed by specific radioimmunoassay of 6-oxo-PGF1alpha(ir-6oxo). Infusion of 0.3,1 and 3 μM acetylcholine (Ach) through the aorta for 7.5 min caused a dose-dependent relaxation of the abdominal ring (33 to 100 % at 3 (μM Ach), indicating intraluminal EDRF release. Maximum relaxation was reached in 3 min and maintained. Release of platelet inhibitory activity was variable. At 3 μM Ach, anti-platelet activity(more than 10 % suppression of aggregation)was present in the effluent of 5 (of 7) aorta's for ADP-, and in effluent of 6 (of 7) aorta's for U46617-induced aggregation. U46619 was more sensitive to the anti-platelet activity, a finding consistent withauthentic PGI2. When a clear anti-platelet activity was monitored, its release was abolished by indo-methacin, which affected neither EDRF release nor platelet aggregation. Baseline release of ir-6oxo was low and variable, but dose-dependently stimulated by Ach, reaching a maximum for each concentration in the 2nd to 3rd minute. In contrast to EDRF, ir-6oxo release was not maintained during the subsequent 4 min and tapered off. Formation of ir-6oxo and anti-aggregatingeffect were positively correlated, but therewas no association between EDRF and ir-6oxo or anti-platelet activity. In conclusion, rabbit aortic endothelium could release EDRF and PGI2, but the present set-up did not reveal an anti-platelet effect of EDRF.

scholarly journals Preclinical studies of RUC-4, a novel platelet αIIbβ3 antagonist, in non-human primates and with human platelets

2019 ◽  
Vol 3 (2-3) ◽  
pp. 65-74 ◽  
Author(s):  
Spandana Vootukuri ◽  
Jihong Li ◽  
Mark Nedelman ◽  
Craig Thomas ◽  
Jiang-Kang Jiang ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Human Platelets ◽  
Initial Slope ◽  
Receptor Blockade ◽  
St Segment Elevation ◽  
St Segment ◽  
Aggregation Inhibition ◽  
Induced Aggregation ◽  
Dose Dependent

AbstractIntroduction:We are developing the novel αIIbβ3 antagonist, RUC-4, for subcutaneously (SC)-administered first-point-of-medical-contact treatment for ST segment elevation myocardial infarction (STEMI).Methods:We studied the (1) pharmacokinetics (PK) of RUC-4 at 1.0, 1.93, and 3.86 mg/kg intravenous (IV), intramuscular (IM), and SC in non-human primates (NHPs); (2) impact of aspirin on RUC-4 IC50in human platelet-rich plasma (PRP); (3) effect of different anticoagulants on the RUC-4 IC50in human PRP; and (4) relationship between αIIbβ3 receptor blockade by RUC-4 and inhibition of ADP-induced platelet aggregation.Results:(1) All doses of RUC-4 were well tolerated, but animals demonstrated variable temporary bruising. IM and SC RUC-4 reached dose-dependent peak levels within 5–15 minutes, with T1/2s between 0.28 and 0.56 hours. Platelet aggregation studies in NHPs receiving IM RUC-4 demonstrated >80% inhibition of the initial slope of ADP-induced aggregation with all three doses 30 minutes post-dosing, with subsequent dose-dependent loss of inhibition over 4–5 hours. (2) The RUC-4 IC50for ADP-induced platelet aggregation was unaffected by aspirin treatment (40±9 nM vs 37±5 nM;p= 0.39). (3) The RUC-4 IC50was significantly higher in PRP prepared from D-phenylalanyl-prolyl-arginyl chloromethyl ketone (PPACK)-anticoagulated blood compared to citrate-anticoagulated blood using either thrombin receptor activating peptide (TRAP) (122±17 vs 66±25 nM;p= 0.05;n= 4) or ADP (102±22 vs 54±13;p<0.001;n= 5). (4) There was a close correspondence between receptor blockade and inhibition of ADP-induced platelet aggregation, with aggregation inhibition beginning with ~40% receptor blockade and becoming nearly complete at >80% receptor blockade.Discussion:Based on these results and others, RUC-4 has now progressed to formal preclinical toxicology studies.

Inhibition Of Platelet Aggregation, Malonyldialdehyde And Thromboxane Formation By Hydroperoxides Of Arachidonic Acid

1981 ◽  
Author(s):  
D Aharonv ◽  
J B Smith ◽  
M J Silver
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Human Platelets ◽  
Lipoxygenase Pathway ◽  
Dose Dependent Fashion ◽  
Induced Aggregation ◽  
Layer Chromatography ◽  
Dose Dependent ◽  
Thromboxane Formation

The arachidonate hydroperoxides 12-HPETE and 15-HPETE were biosynthesized from arachidonic acid using partially purified human platelet lipoxygenase or soybean lipoxidase respectively, and isolated by thin layer chromatography. Both compounds inhibited the arachidonic acid- induced aggregation of washed human platelets, suspended in calcium-free Krebs Henseleit solution, in a dose dependent fashion at concentrations between 1 and 50 uM. No inhibition was seen with up to 100 uM of these hydroperoxides when platelet -rich plasma was used. 12-HPETE (in micromolar concentrations) inhibited the formation of both thromboxane B2 (radioimmunoassay) and malonyldialdehyde (spectrophotometrie assay) when washed platelets were incubated with arachidonic acid. The 12-hydroxide, 12-HETE also inhibited platelet aggregation and thromboxane formation, but was less potent than 12-HPETE. We suggest that arachidonate hydroperoxide generated in platelets via the lipoxygenase pathway modulates platelet aggregation induced by arachidonic acid by inhibiting thromboxane formation.

Endothelium-dependent relaxation and experimental atherosclerosis in the rabbit aorta

1986 ◽  
Vol 64 (11) ◽  
pp. 1451-1453 ◽  
Author(s):  
N. Sreeharan ◽  
R. L. Jayakody ◽  
M. P. J. Senaratne ◽  
A. B. R. Thomson ◽  
C. T. Kappagoda
Keyword(s):  
Rabbit Aorta ◽  
Experimental Atherosclerosis ◽  
Isometric Tension ◽  
Dependent Manner ◽  
Bicarbonate Buffer ◽  
New Zealand White Rabbits ◽  
Set Up ◽  
And Control ◽  
Dose Dependent ◽  
Endothelium Dependent Relaxation

This study was undertaken to determine whether the production or release of the endothelium-dependent relaxatory factor is impaired in atherosclerotic New Zealand White rabbits. Atherosclerosis was induced by feeding a diet containing 2% cholesterol for 6 weeks. The production or release of endothelium-dependent relaxatory factor was assayed as follows. A 5-cm length of aorta donor was perfused with Krebs–bicarbonate buffer and the perfusate drained over a deendothelialized ring of recipient aorta set up for recording isometric tension. The recipient was precontracted with norepinephrine (0.2 μmol/L) in the perfusate. When acetylcholine was added to the perfusate, the recipient relaxed in a dose-dependent manner. This assay was used to compare the relaxatory responses produced in recipient rings by adding acetylcholine to donors from atherosclerotic and control rabbits. The relaxation produced by atherosclerotic donors were smaller than those generated by control donors (16.5 ± 4.9 vs. 32.7 ± 5.3%; n = 10, p < 0.05). It is suggested that in atherosclerotic rabbits the ability of aortic endothelium to produce or release endothelium-dependent relaxatory factor is impaired.

The in-vitro effects of E5555, a protease-activated receptor (PAR)-1 antagonist, on platelet biomarkers in healthy volunteers and patients with coronary artery disease

2009 ◽  
Vol 102 (07) ◽  
pp. 111-119 ◽  
Author(s):  
Motoji Kogushi ◽  
Daniela Dastros-Pitei ◽  
Marcus Flather ◽  
Deepak L. Bhatt ◽  
Victor L. Serebruany
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Healthy Volunteers ◽  
Receptor Expression ◽  
Platelet Activity ◽  
Artery Disease ◽  
In Vitro Effects ◽  
Induced Aggregation ◽  
Dose Dependent

SummaryE5555 is a potent protease-activated receptor (PAR-1) antagonist targeting the G-coupled receptor and modulating thrombinplatelet-endothelial interactions. The drug is currently being tested in phase II trials in patients with coronary artery disease (CAD) and has potential antithrombotic and anti-inflammatory benefits.We investigated the in-vitro effects of E5555 on platelet function beyond PAR-1 blockade in healthy volunteers and CAD patients treated with aspirin (ASA) with or without clopidogrel. Conventional aggregation induced by 5 µM ADP, 1 µg/ml collagen, 10 µM TRAP, whole blood aggregation with 1 µg/ml collagen, and expression of 14 intact, and TRAP-stimulated receptors by flow cytometry were utilised to assess platelet activity after preincubation with escalating concentrations of E5555 (20 ng/ml, 50 ng/ml, and 100 ng/ml) in healthy volunteers, CAD patients treated with ASA, and CAD patients treated with ASA and clopidogrel combination (n=10, for each group). E5555 inhibited a number of platelet biomarkers. Platelet inhibition was usually moderate, present already at 20 ng/ml, and was not seemingly dose-dependent without TRAP stimulation. E5555 caused 10–15% inhibition of ADP- and collagen-induced platelet aggregation in plasma, but not in whole blood.TRAP-induced aggregation was inhibited almost completely. PECAM-1, GP IIb/IIIa antigen, and activity with PAC-1, GPIb, thrombospondin, vitronectin receptor expression, and formation of platelet-monocyte aggregates were also significantly reduced by E5555.TRAP stimulation caused dose-dependent effects between 20 and 50 ng/ml E5555 doses. P-selectin, LAMP-1, LAMP, and CD40-ligand were not affected by E5555. In conclusion, E5555 in vitro moderately but significantly inhibits platelet activity beyond PAR-1 blockade. Antiplatelet potency of ASA alone, and the combination of ASA and clopidogrel may be enhanced by E5555 providing rationale for their synergistic use. Selective blockade of platelet receptors suggests unique antiplatelet properties of E5555 as a potential addition to current antithrombotic regimens.

Antiplatelet Effect of Hsien-Ho-T'sao (Agrimonia Pilosa)

1985 ◽  
Vol 13 (01n04) ◽  
pp. 109-118 ◽  
Author(s):  
Jih-Pyang Wang ◽  
Mei-Feng Hsu ◽  
Che-Ming Teng
Keyword(s):  
Platelet Rich Plasma ◽  
Atp Release ◽  
Water Extract ◽  
Creatine Phosphate ◽  
Inhibitory Effect ◽  
Malondialdehyde Formation ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Induced Aggregation ◽  
Dose Dependent

The water extract of Hsien-Ho-T'sao (HHT) produced a dose-dependent inhibition on collagen-induced aggregation of platelet-rich plasma (PRP). The IC50 was about 3.5 mg/ml. In addition, HHT inhibited also the aggregation induced by ADP, A23187 or arachidonate in PRP. Greater inhibition was observed in the preparation of washed platelets. Increase of the calcium concentration in medium could not overcome the inhibitory effect of HHT. ATP release from platelets induced by collagen or A23187 was inhibited by HHT. In the presence of EDTA, ATP release caused by thrombin or A23187 was also inhibited by HHT. Malondialdehyde and thromboxane B2 formation was greatly inhibited by HHT in platelets challenged by collagen and thrombin. In arachidonate-stimulated platelets, thromboxane B2, but not malondialdehyde formation was inhibited. HHT showed more marked inhibition on aggregation in the presence of indomethacin, creatine phosphate/creatine phosphokinase or a combination of both. Hydrogen peroxide-induced hemolysis was makred reduced by HHT. It was concluded that HHT might have some membrane-active properties which interfered with the activation of phospholipase A2.

Effects of Methylprednisolone and Hydrocortisone on Aggregation of Rabbit Platelets Induced by Arachidonic Acid and Other Aggregating Substances

1981 ◽  
Vol 46 (04) ◽  
pp. 676-679 ◽  
Author(s):  
Frank Glass ◽  
Howard Lippton ◽  
Philip J Kadowitz
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Actual Mechanism ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
The Difference ◽  
Induced Aggregation ◽  
Dose Dependent

SummaryThe effects of methylprednisolone and hydrocortisone on platelet aggregation induced by arachidonic acid (AA), collagen, adenosine diphosphate (ADP), prostaglandin (PG) H2, and a stable PGH2 analog, were studied in platelet-rich plasma (PRP) from the rabbit. Incubation of either steroid in PRP inhibited AA-, collagen- and ADP-induced platelet aggregation in a concentration-related manner. The dose of methylprednisolone required to inhibit 0.02 mM AA-induced aggregation was lower than that required to inhibit either 0.08 μg/ml collagen or 0.2 μM ADP-induced aggregation. Methylprednisolone produced a dose dependent inhibition of platelet aggregation induced by PGH2 and the stable PGH2 analog. In washed platelets methylprednisolone was more effective in inhibiting AA-induced aggregation than ADP- or collagen-induced aggregation; however, the difference in effect was less than in PRP. Platelet responses to AA in PRP from rabbits treated with hydrocortisone or methylprednisolone, 100 mg/kg i.v., were inhibited in a transient manner, whereas aggregation induced by ADP under similar conditions was unchanged. Since inhibition of aggregation elicited by AA occurred at concentrations which do not influence PGH2-, PGH2 analog-, collagen- or ADP-induced aggregation, the present data suggest that the steroids may inhibit the incorporation, the release, or the metabolism of arachidonic acid in platelets. The actual mechanism of this relatively specific inhibition of AA-induced aggregation by anti-inflammatory steroids is uncertain but may be related to the membrane “stabilizing” properties of methylprednisolone and hydrocortisone.

Interaction between ATP and catecholamines in stimulation of platelet aggregation

2003 ◽  
Vol 284 (2) ◽  
pp. H619-H625 ◽  
Author(s):  
Alex V. Birk ◽  
Endri Leno ◽  
Hugh D. Robertson ◽  
Victoria M. Bolotina ◽  
Hazel H. Szeto
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Platelet Reactivity ◽  
Platelet Rich Plasma ◽  
Endothelial Damage ◽  
Clinical Implications ◽  
Induce Platelet Aggregation ◽  
Intracellular Ca ◽  
Dose Dependent ◽  
Stimulation Of

Platelets, on activation by endothelial damage, release ADP, ATP, serotonin, epinephrine, and norepinephrine. Although ATP is known to augment the action of norepinephrine in cardiovascular and endocrine systems, the possible interaction between ATP and catecholamines in regulation of platelet reactivity has not been reported. The addition of ATP (1–5 μM) to human platelet-rich plasma did not induce platelet aggregation; however, it selectively augmented the aggregatory response to norepinephrine and epinephrine, but not to serotonin. This potentiating action of ATP was dose dependent and was not due to contamination by, or hydrolysis to, ADP. The action of ATP was blocked by 10 μM of adenosine 3′-phosphate 5′-phosphosulfate, a selective P2Y1receptor antagonist. ATP alone did not cause release of intracellular Ca2+, but produced a significant Ca2+response in the presence of norepinephrine. In contrast, the P2X1receptor agonists P1,P6-diadenosine-5′ hexophosphate and α,β-methylene-ATP had no effect on norepinephrine-induced platelet aggregation even when added at 100 μM. This synergistic interaction between ATP and norepinephrine in stimulating platelet aggregation may have significant clinical implications and suggests a prothrombotic role for ATP in stress.

SELECTIVE ANTAGONISTS OF PAF: INTERFERENCE WITH PLATELET FUNCTION AND EFFECT ON THROMBOGENESIS INDUCED BY SUBENDOTHELIUM.

1987 ◽  
Author(s):  
P Hadvary ◽  
H R Baumgartner
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Blood Platelets ◽  
Rabbit Aorta ◽  
Constant Infusion ◽  
Induced Aggregation

Platelet activating factor (PAF) is a very potent excitatory agonist of blood platelets but the physiological importance of this mediator in platelet thrombus formation is not known. We investigated the effect of two chemically unrelated selective inhibitors of PAF-induced platelet aggregation on thrombogenesis induced by rabbit aorta subendothelium (SE) using an ex vivo perfusion system.Ro 19-3704 is a highly potent inhibitor structurally related to PAF. This compound inhibits PAF-induced aggregation of rabbit platelets in platelet rich plasma in vitro competitively. Against 4 nM PAF, a concentration resulting in submaximal platelet aggre-gregation velocity, the IC50 was 70 nM. Inhibition was highly selective for PAF-induced aggregation, since aggregation induced by collagen (HORM, 5 yg/ml), ADP (1 yM) or thrombin (0.4 U/ml) was not inhibited even at a concentration as high as 10 yM. Bro-tizolam, a triazolobenzodiazepine reported to be a selective inhibitor of PAF-induced platelet activation, had in our system an IC50 of 200 nM. The selective benzodiazepine antagonist Ro 151788 was without effect on inhibition of PAF-induced platelet activation by brotizolam.Ro 19-3704 was given intravenously to rabbits as a bolus of 0.2 mg/kg followed by constant infusion of 0.02 mg/kg/min. This dosage provoked ex vivo a constant right shift ratio of the dose response curve for PAF-induced aggregation (RSR[PAF]) by a factor of 25 to 35. Brotizolam was given orally at a dose of 100 mg/ kg together with 300 mg/kg of Ro 15-1788 (to antagonize the central effects) 90 minutes before starting the perfusion experiment, resulting in a RSR[PAF] of 35 to 135. ADP induced platelet aggregation was not impaired by either compound. SE was exposed to the non-anticoagulated blood withdrawn from the carotid artery for 3 min at 2600 s-1 and for 20 min at 200 s-1 shear rate. Quantitative morphometric evaluation showed that SE coverage by platelets and by fibrin, thrombus area and thrombus height were all unchanged by the PAF antagonists at low and at high shear rates despite a very substantial inhibition of PAF-induced platelet aggregation. Therefore a major role of PAF in SE-induced thrombogenesis seems unlikely.

scholarly journals PLGA-PEG Nanoparticles Show Minimal Risks of Interference with Platelet Function of Human Platelet-Rich Plasma

2020 ◽  
Vol 21 (24) ◽  
pp. 9716
Author(s):  
Rana Bakhaidar ◽  
Sarah O’Neill ◽  
Zebunnissa Ramtoola
Keyword(s):  
Drug Delivery ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Platelet Activity ◽  
Blood Constituents ◽  
Activation Profile ◽  
The Impact

The expansion of nanotechnology for drug delivery applications has raised questions regarding the safety of nanoparticles (NPs) due to their potential for interacting at molecular and cellular levels. Although polymeric NPs for drug delivery are formulated using FDA-approved polymers such as lactide- and glycolide-based polymers, their interactions with blood constituents, remain to be identified. The aim of this study was to determine the impact of size-selected Poly-lactide-co-glycolide-polyethylene glycol (PLGA-PEG) NPs on platelet activity. The NPs of 113, 321, and 585 nm sizes, were formulated and their effects at concentrations of 0–2.2 mg/mL on the activation and aggregation of platelet-rich plasma (PRP) were investigated. The results showed that NPs of 113 nm did not affect adenosine diphosphate (ADP)-induced platelet aggregation at any NP concentration studied. The NPs of 321 and 585 nm, at concentrations ≥0.25 mg/mL, reduced ADP-activated platelet aggregation. The platelet activation profile remained unchanged in the presence of investigated NPs. Confocal microscopy revealed that NPs were attached to or internalised by platelets in both resting and activated states, with no influence on platelet reactivity. The results indicate minimal risks of interference with platelet function for PLGA-PEG NPs and that these NPs can be explored as nanocarriers for targeted drug delivery to platelets.

scholarly journals Effect of prostaglandin E1 alone and in combination with theophylline or aspirin on collagen-induced platelet aggregation and on platelet nucleotides including adenosine 3′:5′-cyclic monophosphate

1970 ◽  
Vol 120 (4) ◽  
pp. 709-718 ◽  
Author(s):  
G. Ball ◽  
G. G. Brereton ◽  
Mary Fulwood ◽  
D. M. Ireland ◽  
Patricia Yates
Keyword(s):  
Platelet Aggregation ◽  
Cyclic Amp ◽  
Prostaglandin E1 ◽  
Platelet Rich Plasma ◽  
Dependent Manner ◽  
Intracellular Changes ◽  
Induced Aggregation ◽  
Dose Dependent ◽  
Aggregation Of Platelets ◽  
Collagen Treatment

1. Human platelet nucleotides were labelled by incubating platelet-rich plasma with [U-14C]adenine. With such platelets, the effects of prostaglandin E1, theophylline and aspirin were determined on collagen-induced platelet aggregation and release of platelet ATP and ADP. Intracellular changes of platelet radioactive nucleotides, particularly 3′:5′-cyclic AMP, were also determined both with and without collagen treatment. 2. Prostaglandin E1, theophylline and aspirin inhibited collagen-induced aggregation of platelets in a dose-dependent manner. Collagen-induced release of ATP and ADP and breakdown of radioactive ATP were also inhibited in a dose-dependent manner. 3. Prostaglandin E1 stimulated the formation of platelet radioactive 3′:5′-cyclic AMP in a dose-dependent manner. With a given dose of prostaglandin E1, maximum formation of radioactive 3′:5′-cyclic AMP occurred by 10–30s and thereafter the concentrations declined. The degree of inhibition of aggregation produced by prostaglandin E1, however, increased with its time of incubation in platelet-rich plasma before addition of collagen, so that there was an inverse relationship between the radioactive 3′:5′-cyclic AMP concentration measured at the time of collagen addition and the subsequent degree of inhibition of aggregation obtained. 4. Neither theophylline nor aspirin at a concentration in platelet-rich plasma of 1.7mm altered platelet radioactive 3′:5′-cyclic AMP contents. In the presence of prostaglandin E1, theophylline increased the concentration of radioactive 3′:5′-cyclic AMP over that noted with prostaglandin E1 alone, but aspirin did not. 5. Mixtures of prostaglandin E1 and theophylline had a synergistic effect on inhibition of platelet aggregation. The same was true to a lesser extent with mixtures of prostaglandin E1 and aspirin. Such mixtures also inhibited collagen-induced release of platelet ATP and ADP and breakdown of platelet radioactive ATP. 6. Certain concentrations of either theophylline or aspirin and mixtures of small concentrations of prostaglandin E1 with either theophylline or aspirin caused little or no increase of radioactive 3′:5′-cyclic AMP at the time of collagen addition, but inhibited aggregation to a marked degree, whereas higher concentrations of prostaglandin E1 alone caused a much greater increase of radioactive 3′:5′-cyclic AMP at the time of collagen addition but inhibited aggregation to a lesser extent. With these compounds there does not appear to be a correlation between these parameters.

Sign in / Sign up

Export Citation Format

Share Document