Selective Binding Site for [3H]Prostacyclin on Platelets
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The higher affinity binding site for PGI(2) appears to be the specific receptor through which PGI (2) exerts its effect on platelets.Abstract:
Prostacyclin (PGI(2)) is the most potent, naturally occurring inhibitor of platelet aggregation known. To determine whether PGI(2) is bound by platelets, high specific activity [9-(3)H]PGI(2) was synthesized by iodination and subsequent base treatment of the labeled precursor [9-(3)H]prostaglandin (PG)F(2alpha) methyl ester. Binding experiments were performed at room temperature with normal citrated human platelet-rich plasma that contained [(14)C]sucrose or [(14)C]PGF(1alpha) as an internal marker for the extracellular space. Binding of [(3)H]PGI(2) plateaued within 2 min and this bond radioactivity could be displaced rapidly by excess nonradioactive PGI(2). Scatchard analysis of concentration-dependent binding yielded a hyperbolic plot which appeared to be caused by the existence of two classes of binding sites. The higher affinity class has a dissociation constant of 12.1+/-2.7 nM and a capacity of 93 (+/-21)sites per platelet. The lower affinity class had a dissociation constant of 0.909+/-.236 muM and a capacity of 2,700+/-700 sites per platelet. The relative ability of PGI(2), PGE(1), PGE(2), and 6-keto-PGF(1alpha) to displace [(3)H]PGI(2) initially bound to the higher affinity class of sites were 100:5:<0.3: <0.3. These relative abilities parallel the relative potencies of these compounds as inhibitors of ADP-induced platelet aggregation in vitro. However PGD(2), which is more potent than PGE(1) as an inhibitor of aggregation, did not displace bound [(3)H]PGI(2). The higher affinity binding site for PGI(2) appears to be the specific receptor through which PGI(2) exerts its effect on platelets.read more
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Journal Article
International Union of Pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes.
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Prostacyclin is not a circulating hormone in man
TL;DR: The levels of prostacyclin in the plasma of 20 healthy volunteers determined by this assay were much lower than any previously reported and confirms that prostacy Clin is not a circulating hormone in man under normal physiological conditions.
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Thromboxane, prostaglandin and leukotriene receptors.
TL;DR: Thromboxanes, prostaglandins, and leukotrienes are metabolites of the 20-carbon fatty acid arachidonic acid and there is a pressing need to improve the understanding of the fundamental characteristics of these important receptors.
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Prostacyclin inhibits mobilisation of fibrinogen-binding sites on human ADP- and thrombin-treated platelets
Jack J. Hawiger,Jack J. Hawiger,Spencer Parkinson,Spencer Parkinson,Sheila Timmons,Sheila Timmons +5 more
TL;DR: It is reported that prostacyclin inhibits the mobilisation of specific binding sites (‘receptors’) for fibrinogen on human platelets and that this effect parallels the inhibition of ADP- or thrombin-induced aggregation.
References
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Journal ArticleDOI
An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation.
TL;DR: A balance between formation of anti- and pro-aggregatory substances by enzymes could also contribute to the maintenance of the integrity of vascular endothelium and explain the mechanism of formation of intra-arterial thrombi in certain physiopathological conditions.
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Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxides
TL;DR: It is concluded that a balance between formation by arterial walls of PGX which prevents platelet aggregation and release by blood platelets of prostaglandin endoperoxides which induce aggregation is of the utmost importance for the control of thrombus formation in vessels.
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The chemical structure of prostaglandin X (prostacyclin)
Roy A. Johnson,Douglas R. Morton,John H. Kinner,Robert R. Gorman,James C. McGuire,Frank F. Sun,Norman Whittaker,S. Bunting,John A. Salmon,Salvador Moncada,John R. Vane +10 more
TL;DR: The trivial name prostacyclin is proposed for 9-deoxy-6, 9alpha-epoxy-delta5-PGF1alpha, the stable compound formed when prostaglandin X undergoes a chemical transformation in biological systems in 6-keto-PGf1alpha.
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Modulation of human platelet adenylate cyclase by prostacyclin (PGX).
TL;DR: A model of platelet homeostasis is proposed that suggests platelet aggregation is controlled by a balance between the adenylate cyclase stimulating activity of prostacyclin, and the cAMP lowering activity of PGH2.
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Effects of prostacyclin (PGX) on cyclic AMP concentrations in human platelets
TL;DR: Prostacyclin (PGX) strikingly increases cyclic AMP concentrations in human platelets, and these results correlate well with the anti-aggregating activity of prostacyClin, compared with PGE1 and PGD2.