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  • 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 341 (1990), S. 308-315 
    ISSN: 1432-1912
    Schlagwort(e): Prostacyclins ; PGE1 ; PGE2 ; Superoxide anion generation ; gb-Glucuronidase ; cAMP ; Ca2+ ; Human neutrophils ; Platelet activating factor (PAF) ; FMLP
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The action of PGE1, PGE2, PGI2 and iloprost on superoxide anion generation, lysosomal enzyme release, and changes of Ca2+ fluxes in human polymorphonuclear leukocytes (PMN) was studied in vitro. Both PGE-type compounds were equipotent inhibitors of FMLP-and PAF-stimulated superoxide anion generation, β-glucuronidase release (IC50 3–5 μmol/l) and Ca2+ influx while PGI2 and iloprost were ineffective at concentrations up to 10 μmol/l. These inhibitory actions of PGE1 and PGE2 were paralleled by an increase in cAMP level of the PMN while no change occurred with PGI2 and iloprost. None of the prostaglandins affected the initial intracellular Ca2+ liberation after challenge with FMLP or PAF. Preincubation of PMN with PGE1 and PGE2 but not with iloprost resulted in subsequent desensitization against a second administration of these compounds. None of the compounds affected PMN activation produced by arachidonic acid or calcimycin (A 23187). These data demonstrate that PGE-type compounds are effective inhibitors of receptor-mediated (PAF, FMLP) activation of human PMN while prostacyclins are considerably less potent. This suggests that the inhibitory prostaglandin receptor on human PMN belongs to the E-type being functionally different from the inhibitory prostaglandin receptor on human platelets. These results suggest that compounds, such as PGE1 and PGE2 might be superior to prostacyclins to prevent PMN-associated generation of reactive oxygen species and lysosomal enzyme release in situations with endogenous PMN activation, i. e. inflammatory reactions.
    Materialart: Digitale Medien
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 358 (1998), S. 160-167 
    ISSN: 1432-1912
    Schlagwort(e): Key words EP3-receptor ; cAMP ; NFκB ; E-box ; SP1 ; AP2
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A cDNA clone, encoding a complete porcine EP3 receptor, was isolated from a porcine heart cDNA library. The deduced amino acid sequence revealed a protein of 387 amino acid residues with an estimated molecular weight of 43 kD and strongest homology to the human EP3-II receptor (84% identity on protein level). Ligand binding studies with transfected COS-7 cells, expressing the porcine receptor, showed displacement of [3H]PGE1 with the EP3-specific agonist M & B 28.767, the EP1/EP3-agonist sulprostone but not with the EP2-specific agonist butaprost. Stimulation of transfected CHO cells with M & B 28.767 resulted in inhibition of forskolin-induced cAMP formation, suggesting coupling to an inhibitory G protein. Agonist-induced translocation of the transcription factor NFκB into the nucleus of transfected CHO cells was demonstrated by Western blot analysis, indicating that these EP3 receptors modulate NFκB-dependent cellular signal transduction. Analysis of the genomic organization identified the major transcription initiation site at about 160 bp upstream of the ATG start codon. The 800-bp 5’ flanking region contains a variety of putative cis-acting regulatory elements, including binding sites for AP2, SP1 and MyoD (E-box). The present data will now allow further studies on EP3 receptor-mediated signal transduction and its regulation.
    Materialart: Digitale Medien
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  • 4
    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
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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
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 302 (1978), S. 61-62 
    ISSN: 1432-1912
    Schlagwort(e): Isolated guinea pig heart ; Coronary vascular resistance ; Myocardial force of contraction ; Prostaglandin D2 (PGD2)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The action of prostaglandin D2 (PGD2) on myocardial force of contraction (MFC) and coronary vascular resistance (CVR) was studied in the isovolumetrically perfused guinea pig heart at constant driving frequency (180 beats/min). PGD2 (2·10−9–1·10−6 M) produced a concentration-dependent increase in the CVR while the MFC remained unchanged. The ED50 (50% of maximum response) of the coronary vasomotor action amounted to 4.3 ·10−8 M PGD2. The results give evidence for a potent coronary vasoconstrictor activity of PGD2.
    Materialart: Digitale Medien
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  • 7
    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
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 313 (1980), S. 69-75 
    ISSN: 1432-1912
    Schlagwort(e): Thromboxane A2 (TXA2) ; Prostacyclin (PGI2) ; Human platelets ; Bovine coronary artery ; Non-steroidal antiinflammatory drugs ; Prostaglandin-cyclooxygenase ; Bioassay ; RCS
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The action of the non-steroidal antiinflammatory drugs indomethacin, tiaprofenic acid, diclofenac and meclofenamate on vascular and plateletcyclooxygenases was studied by measuring the arachidonic acid-induced thromboxane A2 (TXA2)-formation of washed human platelets and prostacyclin (PGI2)-formation of bovine coronary artery rings. TXA2 was bioassayed as RCS on rabbit aorta strips, PGI2 in terms of its antiaggregatory activity on ADP-induced aggregation of human platelet-rich plasma. All of the substances studied produced concentration-dependent inhibition of PGI2- and RCS-release. The IC50 [μM] in inhibition of RCS-formation was 0.019 for indomethacin, 0.070 for tiaprofenic acid but 44.9 for meclofenamate and 63.2 for diclofenac. The IC50 [μM] in inhibition of PGI2-release was 0.42 for diclofenac, 0.63 for indomethacin and 0.99 for tiaprofenic acid. The data suggest (1) high sensitivity of human platelet-cyclooxygenase against indomethacin and tiaprofenic acid, (2) different sequence of the substances studied in inhibiting arachidonic acid-induced TXA2- and PGI2-formation. The possible therapeutic value of selective inhibition of platelets and vascular cyclooxygenases in discussed.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 9
    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
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  • 10
    Digitale Medien
    Digitale Medien
    Copenhagen : International Union of Crystallography (IUCr)
    Acta crystallographica 51 (1995), S. 1099-1102 
    ISSN: 1399-0047
    Quelle: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Thema: Chemie und Pharmazie , Geologie und Paläontologie , Physik
    Notizen: Microgravity offers an environment for protein crystallization where there is an absence of convection and sedimentation. We have investigated the effect of microgravity conditions on the perfection of protein crystals. The quality of crystals for X-ray diffraction studies is characterized by a number of factors, namely size, mosaicity and the resolution limit. By using tetragonal lysozyme crystals as a test case we show, with crystal growth in two separate Space Shuttle missions, that the mosaicity is improved by a factor of three to four over earth-grown ground control values. These microgravity-grown protein crystals are then essentially perfect diffraction gratings. As a result the peak to background of individual X-ray diffraction reflections is enhanced by a similar factor to the reduction in the mosaicity. This then offers a particularly important opportunity for improving the measurement of weak reflections such as occur at high diffraction resolution. These microgravity results set a benchmark for all future microgravity and earth-based protein crystallography procedures.
    Materialart: Digitale Medien
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