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  • Cyclic AMP  (2)
  • Prostacyclin  (2)
  • Antiplatelet actions  (1)
  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1997), S. 10-16 
    ISSN: 1432-1912
    Schlagwort(e): Key words Thromboxane A2 receptor ; Cloning ; Expression ; Radioligand binding ; Cyclic AMP
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract This study describes the molecular cloning and functional characterization of the bovine thromboxane A2 (TP) receptor. Two partial nucleotide sequences coding for the bovine TP receptor were isolated from a bovine genomic and a bovine heart cDNA library. The deduced amino acid sequence suggests a heptahelical protein of 343 amino acids. The receptor protein is homologous with that of human placenta and endothelium at 84.0% and 81.4%, respectively. COS-7 cells were transfected with the bovine TP receptor cDNA, and binding affinities were assessed by radioligand binding studies. Specific displacement of [3H]SQ 29548 was demonstrated in COS-7 cell membranes with the unlabeled TP receptor antagonist SQ 29548 (K d = 12.6 ± 1.1 nM) and the TP receptor agonist U46619 (K d = 192.1 ± 58.9 nM), but not with other prostaglandins (PGD2, PGE1, PGF2α), or the PGI2 mimetic cicaprost. Agonist-induced stimulation of adenylyl cyclase in transfected COS-7 cells indicates a linkage to the cAMP signal transduction pathway via coupling to a stimulatory G-protein. Since bovine cells, e.g. vascular smooth muscle cells, are an established model to study the role of eicosanoids in cell signaling, this report on the molecular structure of the bovine TP receptor will allow further studies on receptor regulation.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular medicine 64 (1986), S. 545-551 
    ISSN: 1432-1440
    Schlagwort(e): Iloprost ; Antiplatelet actions ; Blood pressure ; Regional perfusion ; Peripheral arterial obliterative disease (PAOD) ; Dose-response study ; Controlled trial
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The dose-dependent inhibition of platelet aggregation by the chemically stable, prostacyclin-mimetic, iloprost, was studied in patients suffering from stage II–III peripheral arterial obliterative disease (PAOD). The study was designed as a randomized placebo-controlled cross-over trial. Iloprost was administered i.v. to six patients at doses of 0.5, 1.0, 2.0 or 3.0 ng/kg×min for 4 h, with an interval of 2–3 days between the infusions. During iloprost infusion, systolic and diastolic arterial blood pressure, heart rate and blood flow in the affected limb remained unchanged. In contrast, there was a considerable, dose-dependent inhibition of ADP- and thrombin-induced platelet aggregation and secretion ex vivo at doses of 0.5–2.0 ng/kg×min iloprost, indicating that iloprost reduced platelet stimulation by 50%–70%. The antiplatelet action of iloprost remained unchanged during infusion but ceased with 2 h after administration had ended. The agent was tolerated by the patients without unacceptable side-effects at doses up to 2 ng/kg × min. It is concluded that iloprost administered i.v. at doses of 1–2 ng/kg×min in patients with stage II–III PAOD does not involve haemodynamic side-effects and might be considered an effective antiplatelet agent.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular medicine 61 (1983), S. 363-367 
    ISSN: 1432-1440
    Schlagwort(e): Plasmapheresis ; Hemolytic-uremic syndrome ; Prostacyclin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Three children with hemolytic-uremic syndrome (HUS) were successfully treated with plasmapheresis (PP) combined with early hemodialysis and administration of Aspirin and dipyridamole. Stimulation of vascular prostacyclin release with patients' plasma was measured before and after PP. It was reduced before and increased after plasma exchange. The data indicate that PP might be a useful tool in treatment of (HUS) in children.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 306 (1979), S. 101-103 
    ISSN: 1432-1912
    Schlagwort(e): Prostacyclin (PGI2) ; Cyclic AMP ; Adenosine ; Noradrenaline ; Coronary arteries
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The effects of prostacyclin (PGI2) on vascular tension and cAMP content were measured in isolated bovine coronary artery strips. 3 nM PGI2 did not alter the tension but diminished the cAMP content by 56% of the control level (P〈0.005). 30 and 300 nM PGI2 diminished the tension and further reduced the cAMP content, which amounted to only 5% of the control at 300 nM PGI2. These results are in contrast to the increase in cAMP level by PGI2 in blood platelets and might indicate a different mechanism of action of PGI2 in platelets and vascular tissue.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 316 (1981), S. 252-255 
    ISSN: 1432-1912
    Schlagwort(e): Carbacyclin-Derivative ; Prostacyclin ; ZK 36 374 ; Vessel tone ; Platelet aggregation ; Platelet disaggregation ex vivo ; Blood pressure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The vascular and antiplatelet activities of a new, chemically stable carbacyclin derivative (ZK 36 374) were investigated and compared to PGI2. ZK 36 374 dose-dependently relaxed bovine coronary artery strips in vitro but was without direct effects on strips of bovine coronary veins which were contracted by PGI2. ZK 36 374 dose-dependently inhibited the ADP-, thrombin- and collagen-induced platelet aggregation in human platelet-rich plasma and disperded preformed platelet aggregates in whole blood of cats ex vivo. The IC50 was 0.2–1.1 (antigaggregation) and 13 (disaggregation) nM, respectively, and in the same range as PGI2. The maximum antiplatelet dose of ZK 36 374 (resolution of platelet aggregates) in anaesthetized cats in vivo was 0.45 nmoles/kg x min, and could be increased up to 3 nmoles/kg x min, i.e. 6–7-fold without significant changes in arterial blood pressure and heart rate. This indicates an appreciable dissociation between antiplatelet and blood pressure-lowering activities of this compound, at least in this model. It is concluded that ZK 36 374 is the first, chemically stable prostacyclin-mimetic agent that is equipotent to PGI2 in vitro and might be superior to PGI2 in vivo because of a reduced blood pressure-lowering activity.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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