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  • Title: Dissociation of theophylline uptake and inotropic effect in myocardial tissue: influence of temperature, pH and calcium.
    Author: Bellemann P, Scholz H.
    Journal: Br J Pharmacol; 1975 May; 54(1):75-81. PubMed ID: 237594.
    Abstract:
    1. The myocardial uptake and the positive inotropic effect of theophylline (100 mug/ml; 0.56 mM) were studied in isolated electrically driven guinea-pig hearts perfused by the Langendorff technique under various extracellular conditions. [3H]-theophylline was used. 2. Variations in temperature, hydrogen ion and calcium ion concentrations of the perfusion media changed the time course and magnitude of the effect of theophylline on myocardial twitch tension but did not affect the time course and amount of theophylline uptake. 3. Under all conditions, the build-up of the positive inotropic effect of theophylline was about three times faster than the uptake of the drug into the heart. 4. Since no relationship could be found between theophylline uptake and inotropic effect, the cardiac positive inotropic response to theophylline is thought unlikely to be due mainly to an interaction of the drug with intracellular receptor sites but is assumed to occur via an effect of the drug on the sarcolemma, that is at a site which the drug reaches before it enters the intracellular space.
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