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  • 1
    ISSN: 1432-1912
    Keywords: Papaverine ; Isoprenaline ; cAMP ; Contractility ; Frequency of stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Responses to papaverine and isoprenaline on cyclic AMP and contractility were investigated in left atria of guinea-pigs driven at a rate of 0.5 or 2 Hz. 1. Studies on the time course of the effects of isoprenaline (3×10−8 M) showed that the increase in cAMP levels preceded the increase in contractile activity. cAMP increased to maximal values and then rapidly fell to the control levels with a similar time course both at 0.5 and 2 Hz. The contractile responses to isoprenaline, however, showed a different time course. The development of the inotropic response to isoprenaline occurred faster at 2 Hz than at 0.5 Hz. In contrast to the levels of cAMP maximal contractile responses were maintained throughout the presence of isoprenaline. 2. At a stimulation frequency of 2 Hz with increasing concentrations of papaverine (10−6 M, 3×10−6 M, 3×10−5 M) the cAMP content increased dose-dependently. However, no correlation between the effects on cAMP and contractility could be established since 3×10−5 M papaverine already reduced contractile amplitude. The same concentration of papaverine slightly depresssed the inotropic responses to isoprenaline whereas it considerably enhanced the effects of isoprenaline on cAMP. 3. At a stimulation frequency of 0.5 Hz papaverine produced similar effects on the basal cAMP level and the cAMP responses to isoprenaline as at 2 Hz. However, papaverine increased significantly cardiac contractility and potentiated the positive inotropic effects of isoprenaline. At this rate of stimulation a linear relationship between the positive inotropic effect and the increase in cAMP as produced by increasing concentrations of papaverine (10−6 M, 3×10−6 M, 3×10−5 M) was obtained. The dissociation of the effects of papaverine on contractility and cAMP seems to be related to a calcium antagonistic property which—in addition to the inhibition of phosphodiesterase—comes into play at higher rates of beat and inhibits the effects of elevated cAMP on myocardial contractility.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1912
    Keywords: α-and β-Adrenoceptors ; Methoxamine ; Isoprenaline ; cAMP ; Papaverine ; Rabbit Papillary Muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the isolated papillary muscle of the rabbit the time course of the effects of selective β-and α-adrenoceptor stimulation by isoprenaline and methoxamine, respectively, on the contractile force and on the level of 3′,5′-cyclic AMP (cAMP) was determined. 1. Isoprenaline (3×10−7 M) increased significantly the content of cAMP at 15 sec and elevated it to the maximal level-about twice the control value-at 30 sec after its administration, while the developed tension of the papillary muscle was also increased significantly at 15 sec and reached gradually its maximum at 90 sec. 2. Compared with isoprenaline methoxamine (10−4 M) increased the developed tension very slowly: the maximal response was reached after 20 min. The level of cAMP, on the other hand, was changed neither before nor during the induction of the positive inotropic effect of methoxamine. 3. The phosphodiesterase inhibitor papaverine (10−5 M) inhibited the PDE activity of the papillary muscle by about 40% after an incubation of 1 hr, and increased the level of cAMP significantly. The effects of isoprenaline on the contractile force and on the level of cAMP were considerably enhanced by papaverine: the content of cAMP was increased by isoprenaline (3×10−7 M) to about 3 times the control value and also its positive inotropic effect was significantly greater than in controls without papaverine. On the other hand, the positive inotropic effect of methoxamine (10−4 M) was not affected by papaverine (10−5 M). Further-more, in the papillary muscle treated with papaverine the level of cAMP was significantly reduced by methoxamine: the papaverine-induced increase of cAMP was abolished by methoxamine. 4. The present results are compatible with the hypothesis that cAMP is involved as a mediator in the positive inotropic effect induced by β-adrenoceptor stimulation, and indicate further that the stimulation of α-adrenoceptors evokes its positive inotropic effect through a mechanism other than that elicited by β-adrenoceptor stimulation, i.e., independent of cAMP.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 308 (1979), S. 19-23 
    ISSN: 1432-1912
    Keywords: Dobutamine ; Isoprenaline ; Terbutaline ; Guinea-pig atrium ; Guinea-pig trachea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experiments with the dopamine-congener dobutamine were performed on isolated, spontaneously beating right atria as well as on electrically driven left atria of guinea pigs (2 and 3 Hz). Furthermore, its relaxant effect on the tracheal chain was investigated. 1. On right atria dobutamine caused a positive chronotropic effect, the corresponding pD2-value was by 1.75 log units lower than that determined for isoprenaline. The intrinsic activity (isoprenaline=1) was 0.79 for the increase in rate. The pA2-value characterizing the antagonism between metoprolol and dobutamine or isoprenaline for the positive chronotropic effect were comparable indicating that the effects are mediated by the same type of β-adrenoceptor. 2. On the left atrium driven at 2 Hz the pD2-value for the positive inotropic effects of dobutamine and isoprenaline was by 1.82 log units lower for dobutamine than for isoprenaline. The intrinsic activity of dobutamine amounted to 0.62 (isoprenaline=1.0). The pA2-values of metoprolol, on the other hand, did not differ significantly in the presence of either dobutamine or isoprenaline. 3. Since the right atria developed a spontaneous rate of about 3 Hz, left atria were also driven at 3 Hz. The pD2-values of dobutamine under these conditions were 6.05 for the positive chronotropic effect obtained on right atria and 6.07 for the positive inotropic effect obtained on left atria, also the pA2-values determined for metoprolol showed no significant differences. 4. Dobutamine completely relaxed the guinea-pig tracheal chain preparation, its intrinsic activity was identical with that of isoprenaline. The pD2-value amounted to 5.38, that determined for isoprenaline was 7.86. The corresponding pA2-values for metoprolol did not differ from each other: in the presence of dobutamine it amounted to 6.55, while for isoprenaline it was 6.50. 5. By stimulation of cardiac β1-adrenoreceptors dobutamine causes — like isoprenaline — positive inotropic and chronotropic effects of comparable degree. The tracheal β2-adrenoreceptors are also stimulated by dobutamine; the pD2-value for tracheal relaxation was by about 0.69 log units lower than that for cardiostimulation.
    Type of Medium: Electronic Resource
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