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  • Guinea pig heart  (2)
  • coronary vessels  (2)
  • AP2  (1)
  • 1
    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
    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
    ISSN: 1435-1803
    Schlagwort(e): prostacyclin ; thromboxane ; platelets ; coronary vessels ; arachidonic acid
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary A new experimentalin-vitro model is described, which was used for studying prostacyclin (PGI2)-thromboxane A2 (TXA2)-interactions. Langendorff hearts of guinea pigs are perfused at constant volume with Krebs-Henseleit buffer and washed human platelets (4x108/min). PGI2 and TXA2 release are measured by bioassay. The cardiac and coronary function and the myocardial oxygen consumption are continuously monitored. The platelet count in the cardiac effluent can be measured and the cAMP content has been estimated. This model might be a useful tool for studying the roles of PGI2 and TXA2 in platelet activation and coronary perfusion in terms of endogenously synthesized substances.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Basic research in cardiology 76 (1981), S. 239-249 
    ISSN: 1435-1803
    Schlagwort(e): heart ; myocardial ischemia ; prostacyclin (PGI2) ; thromboxanes ; coronary vessels ; cyclic AMP
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Prostaglandine können als eine Gruppe chemischer Substanzen angesehen werden, die lokal entstehen und die koronare Perfusion an die Stoffwechselerfordernisse des Herzens anpassen. Vorliegende Arbeit gibt eine Zusammenfassung des heutigen Wissensstandes auf diesem Gebiet unter besonderer Berücksichtigung von Prostacyclin (PGI2). Neben Biosynthese und Metabolismus sowie ihrer Beeinflussung durch Pharmaka werden kardiale und koronare Wirkungen von PGI2 beschrieben und mögliche Wirkungsmechanismen der Substanz unter physiologischen und pathophysiologischen (myokardiale Ischämie) Bedingungen diskutiert. Im Mittelpunkt stehen Wechselwirkungen zwischen PGI2, Adenosin und Katecholaminen und ihre möglichen Konsequenzen für die Regulation des koronaren Tonus. Hierzu wird ein Modell vorgestellt, bei dem die direkt-vasokonstriktorischen und stoffwechselsteigernden Katecholaminwirkungen durch Bildung von PGI2 im Gefäßbereich und Adenosin im Herzmuskelstoffwechsel funktionell antagonisiert werden.
    Notizen: Summary Prostaglandins may represent one group of local chemical factors that control coronary perfusion and adapt it to the metabolic demands of the heart. Present study summarizes the current knowledge in this field with particular reference to prostacyclin (PGI2). The major biosynthetic pathways and their modification by drugs are briefly outlined. The sources and fates of cardiac prostaglandins are described and possible mechanisms of action discussed in both physiological and pathophysiological (myocardial ischemia) situations. Attention is focussed on the interplay between catecholamines, adenosine and PGI2. A model is presented, based on the hypothesis that adenosine from myocardial metabolism and PGI2 from vascular sites are acting in concert to antagonize sympathetic metabolic and vasoconstrictory influences and to maintain an adequate blood supply to the heart.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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