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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 279 (1973), S. 313-325 
    ISSN: 1432-1912
    Keywords: Dibutyryl-c-AMP ; Adrenaline ; Isolated Rat and Guinea-Pig Auricles ; Positive Inotropic Effect ; 45Ca Exchange
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The positive inotropic effect of adrenaline has been assumed to result from an increase in the intracellular level of c-AMP which, in turn, might enhance the permeability of the cardiac cell membrane to Ca2+. In order to further test this hypothesis, the effects of cyclic N6-2′-O-dibutyryl-adenosine-3′,5′-monophosphate (DB-c-AMP; 10−3 M) on mechanical performance, 45Ca uptake and total tissue calcium concentration were investigated in electrically stimulated (120 beats/min) left auricles isolated from female rats weighing 180–220 g. The experiments were performed in Tyrode solution containing 0.9 mM CaCl2; the duration of 45Ca exposure was 3–60 min. In this study, DB-c-AMP markedly enhanced contractile force but the drug failed to detectably increase 45Ca exchange (Figs. 1 and 2). This finding seemed to indicate that the effects of DB-c-AMP on myocardial 45Ca exchange were completely different from those of adrenaline which previously (and in this study; Fig. 4) has been shown to accelerate 45Ca exchange in auricles obtained from guinea-pigs of “normal” size. However, under the conditions used, adrenaline (2.2–5.5×10−6 M) also failed to significantly enhance 45Ca exchange not only in rat auricles (Fig. 3) but also in small auricles isolated from very light guinea-pigs (body-weight 75–150 g; Fig. 4). From these findings it is concluded that druginduced changes in membrane calcium fluxes, which possibly occur, only might have escaped detection under the present experimental conditions. The “pool saturation phenomenon” previously described by Grossman and Furchgott (1964b; 1964c) is discussed to be the underlying mechanism. Thus, substantial conclusions on the effects of DB-c-AMP on myocardial Ca fluxes can as yet not be drawn. They must await experiments in which an adrenaline induced increase in cardiac 45Ca exchange becomes detectable.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1912
    Keywords: Dibutyryl-c-AMP ; Adrenaline ; Isolated Rat Auricles ; Positive Inotropic Effect ; 45Ca Exchange
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of adrenaline (2.2×10−6 M) and cyclic N6-2′-O-dibutyryl-adenosine-3′,5′-monophosphate (DB-c-AMP; 10−3 M) on mechanical performance, 45Ca uptake and total tissue calcium concentration were investigated in electrically stimulated left auricles isolated from female rats weighing 180–220 g. The experiments were performed at reduced [Ca]e of 0.45 mM and at various frequencies of stimulation (0–120 beats/min). In the first series of experiments 45Ca incubation time was 5 min. Under these conditions DB-c-AMP as well as adrenaline enhanced contractile force to 300–450% of the control values at all frequencies tested (Fig.1). This increase in contractile force was accompanied by a significant enhancement in 45Ca exchange (Fig.2) while the total tissue calcium concentration remained unchanged (Table 1). In resting auricles 45Ca exchange was not altered under the influence of both drugs. At long periods of 45Ca exposure (40–90 min) both drugs augmented contractile force in a way similar to that of the first series of experiments (Fig.4) but no influence of DB-c-AMP or adrenaline on 45Ca exchange could be detected (Fig.3). It is concluded that DB-c-AMP can mimic the wellknown effects of adrenaline on myocardial calcium movements. Under the assumption that DB-c-AMP is representative for c-AMP, the results thus provide experimental support for the view that the positive inotropic effect of adrenaline is mediated by primary changes in the intracellular level of c-AMP which secondarily might enhance calcium fluxes across the cardiac cell membrane.
    Type of Medium: Electronic Resource
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