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  • Cyclic AMP  (2)
  • Guinea pig heart  (2)
  • Antiplatelet actions  (1)
Materialart
Erscheinungszeitraum
  • 1
    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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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 306 (1979), S. 213-217 
    ISSN: 1432-1912
    Schlagwort(e): Dihydro-PGI2 ; Prostacyclin (PGI2) ; Bovine coronary artery ; Guinea pig heart ; Myocardial mechanics ; Coronary vascular tone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The action of the dihydro prostacyclins, (6R)-PGI1 and (6S)-PGI1, was studied on the isolated guinea pig heart and bovine coronary artery strips. PGE2 and PGI2 were used as standards. In the isolated guinea pig heart (6S)-PGI1 decreased the coronary perfusion pressure (CPP), myocardial force of contraction (MFC) and oxygen consumption (QO2). (6R)-PGI1 did not produce a significant change in these parameters. The ED50 (50% of maximum coronary dilation) was approximately 20 times higher for (6S)-PGI1 than for PGI2 or PGE2. Treatment of the hearts with reserpine + tyramine abolished the (6S)-PGI1-induced decrease in MFC but not the decrease in the CPP. The same pattern of responses was seen with PGE2. Bovine coronary artery strips were contracted by both (6S)-PGI1 and (6R)-PGI1, the ED50 (50% of maximum increase in tension) being 5 and 10 times higher than that for PGE2. The (6S)-PGI1-induced contraction was preceeded by a small relaxation, which, however, was much less than that seen after PGI2. It is concluded that the hydration of the 5,6 double bound in the PGI2-like activity and generates PGE-like activity. The same biological activity of both dihydro prostacyclins in the isolated coronary artery strip but not in the intact coronary vascular bed leads to suggest that the sites of action in these systems are different.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 307 (1979), S. 213-221 
    ISSN: 1432-1912
    Schlagwort(e): Prostacyclin (PGI2) ; Bradykinin ; Coronary artery ; Guinea pig heart ; Indomethacin ; Oxygen consumption ; Myocardial mechanics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 1. The action of bradykinin on prostacyclin (PGI2) release and the coronary artery tone was studied in the isolated guinea pig heart and the bovine coronary artery. Myocardial force of concentration and oxygen consumption were monitored continuously. 2. Addition of bradykinin to the guinea pig heart was followed by a dose-dependent decrease in the coronary perfusion pressure, while myocardial contractile force and oxygen consumption remained unchanged, indicating a direct effect on the coronary vascular resistance. There was no evidence for tachyphylaxis. 3. Long-term treatment of the hearts with indomethacin at low concentrations (5×10−7 g/ml) did not influence the bradykinin-induced coronary dilation. Increasing the indomethacin (5×10−6 g/ml) produced a partial (repetitive application) or complete inhibition (cumulative dose-response curves). 4. Application of bradykinin to coronary artery strip also produced relaxation. Indomethacin (2×10−6 g/ml) did only attenuate this effect although it completely prevented the response to arachidonic acid. 5. The release of PGI2-like material from the heart by bradykinin was studied using the cascade-technique of Vane (1969). There was a dose-dependent release of a substance, which relaxed the bovine coronary artery. Pretreatment of the hearts with 15-hydroperoxy arachidonic acid or indomethacin (5×10−6 g/ml) produced a partial or complete inhibition of this response. However, there was no significant inhibition of the bradykinin-induced relaxation of the coronary vascular bed. 6. It is suggested that the inhibitory effect of high dose indomethacin is not due to inhibition of prostaglandin biosynthesis, which is already completely blocked at low doses. According to this, two different actions of indomethacin on the coronary vessels could be established. 7. The results indicate that bradykinin produces a pronounced release of PGI2 from the coronary vessels, which, however, can be blocked without abolition of the coronary relaxing activity. This provides evidence for an additional, PGI2-independent coronary action of this substance.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    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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  • 5
    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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