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  • 1
    ISSN: 1432-1912
    Keywords: Calcium ; Noradrenaline ; ß-Blockers ; Quinidine ; Guinea-pig auricles. ; Calcium ; Noradrenalin ; ß-Adrenolytica ; Chinidin ; Meerschweinchenvorhof
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Isometrische Kontraktionen von elektrisch konstant gereizten linken Meerschweinchenherzohren wurden unter Einwirkung von Noradrenalin, MHIP, Pronethalol und Chinidin bei extracellulären Calciumkonzentrationen ([Ca] e ) zwischen 0,45 und 7,2 mM untersucht. Noradrenalin führte gegenüber den Kontrollwerten bei verschiedenen [Ca] e zu einer Linksverschiebung der Calcium-Konzentrations-Wirkungskurve. Für die ß-Adrenolytica MHIP und Pronethalol zeigte sich eine Abhängigkeit ihrer negativ inotropen Wirkung von der [Ca] e . In niedriger [Ca] e fand sich eine stärkere Verminderung der Kontraktionsamplitude als in höherer [Ca] e . Die Wirkung von Chinidin auf die Kontraktionskraft der Vorhöfe war von der [Ca] e unabhängig. Die ß-adrenolytische Wirkung von MHIP und Pronethalol bei Kombination mit Noradrenalin war bei allen untersuchten [Ca] e gleich. Außer bei 0,45 mM [Ca] e hatte Chinidin keine Wirkung auf den positiv inotropen Noradrenalineffekt.
    Notes: Summary Isometric contractions of electrically driven (180/min) left guinea-pig auricles were recorded under the influence of norepinephrine, ß-blocking agents and quinidine at different extracellular calcium concentrations ([Ca] e ) between 0.45 to 7.2 mMol/l. Norepinephrine shifted the concentration-response curve for calcium to the left. The negativ inotropic effects of the ß-blocking agents MHIP and pronethalol depended on the [Ca] e . At low [Ca] e the force of contraction decreased to a larger extent than at high [Ca] e . The action of quinidine on the contractile force of the guinea-pig auricles was independent of the [Ca] e . The ß-adrenergic blocking action of MHIP and pronethalol was the same at all [Ca] e .
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 321 (1982), S. 89-99 
    ISSN: 1432-1912
    Keywords: β-Adrenoceptors ; Intact heart cells ; Carazolol ; CGP 12177 ; Agonist affinity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have used primary cultures of hearts from newborn rats to study β-adrenoceptor properties in living myocardial cells. Receptors were labelled with the lipophilic antagonists 3H-(±)-carazolol and 125I-(±)-cyanopindolol (CYP) or with the hydrophilic antagonist 3H-(±)-CGP 12177. Under equilibrium conditions all ligands bound to a saturable homogeneous class of specific sites with a maximal binding capacity of ∼ 100 fmol/mg protein (corresponding to ∼ 5000 sites/cell). After 90–180 min preincubation of intact cells with 3H-carazolol or 3H-CGP 12177 only 80% of these antagonists could be displaced from specific binding sites by competing ligands. In the simultaneous presence of the antagonist (-) timolol 100% of specifically bound radiolabelled ligand remained displaceable. In competitive displacement experiments the radioligands did not affect the apparent affinity of the displacing nonlabelled antagonists timolol and CGP 12177, but agonist affinity was markedly changed. The apparent K D values for (-)-isoprenaline were 1560 and 2720 nmol/l in the presence of carazolol and CYP, but only 32 nmol/l in the presence of CGP 12177. This antagonist-dependent difference in agonist K D values was observed only in intact cells but not in membrane particles prepared from heart homogenates of newborn rats, where high agonist affinity was seen during displacement of all radioligands. The K A value for isoprenaline-stimulated cAMP accumulation in living cells was 30 nmol/l in 5-day cultures. A direct proportionality existed between agonist receptor occupation and cAMP accumulation in the presence of CGP 12177 as estimated by the K A/K D ratio. In the presence of carazolol the K A/K D ratio decreased from 1 to 0.02 suggesting that low affinity receptors were not coupled functionally to adenylate cyclase. These results indicate that some lipophilic antagonists which appear to be inert competitive ligands in fragmented membranes, alter receptor binding properties in intact cells. These antagonists seem to promote the transformation of receptor sites into a new “inactivated” state where competitive interactions between different ligands are inhibited.
    Type of Medium: Electronic Resource
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