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  • 1
    ISSN: 1432-1912
    Keywords: Human right atrial β1-adrenoceptors ; Human right atrial β2-adrenoceptors ; Cyclic AMP ; Contractility ; Human heart
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The time course of the effects of isoprenaline (3 × 10−7 mol/l) on contractile force and on the cyclic AMP level was studied in the electrically driven isolated muscle strip of the human right atrium. Isoprenaline produced a rise in cyclic AMP content (maximum increase after 60 s) preceding the increase in contractile force. The effects of isoprenaline on contractile force and on the intracellular level of cyclic AMP were enhanced in the presence of the phosphodiesterase inhibitor papaverine (10−5 mol/l). On the other hand, the β-adrenoceptor antagonist propranolol (10−7 mol/l) suppressed isoprenaline-induced cyclic AMP increases, but reduced the increase in force of contraction by only 35%. In addition, both the β1-selective antagonist bisoprolol (3 × 10−9 × 10−8 mol/l) and the β2-selective antagonist ICI 118,551 (3 × 10−9 × 10−8 mol/l) inhibited the isoprenaline-induced cyclic AMP increase concentration-dependently; ICI 118,551 produced more pronounced inhibition than bisoprolol. It is concluded that cyclic AMP is involved in the positive inotropic action of isoprenaline evoked by β1- and β2-adrenoceptor stimulation in isolated human right atrium; however, an additional cyclic AMP independent mechanism cannot be ruled out.
    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
    ISSN: 1432-1912
    Keywords: α-Adenoceptors ; β-Adrenoceptors ; Phenylephrine ; cAMP ; Papaverine ; Rabbit papillary muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The time course of changes of the level of 3′,5′-cyclic AMP (cAMP) and of the tension developed under stimulation of α- and β-adrenoceptors by phenylephrine was investigated in the isolated rabbit papillary muscle. Furthermore the doseresponse relationships for increases of cAMP and of developed tension elicited by phenylephrine were determined. 1. A submaximally effective concentration of phenylephrine (10−5 M) increased significantly the level of cAMP of the papillary muscle at 15 and 30 s by 45 and 36%, respectively; the level of cAMP returned to the control value at 60 s after the administration. The developed tension increased significantly not before 45 s and reached its maximal level at 180 s. 2. When α-adrenoceptors were blocked by phentolamine (10−6 M), the positive inotropic effect of phenylephrine was decreased significantly but the increase of cAMP induced by phenylephrine was not reduced. In the presence of phentolamine the increase of cAMP induced by phenylephrine lasted longer than in the control experiments. 3. The effects of phenylephrine (10−5 M) both on the level of cAMP and the developed tension mediated via stimulation of β-adrenoceptors in the presence of phentolamine were enhanced by the phosphodiesterase inhibitor papaverine throughout the course of responses. 4. Phenylephrine produced an increase in developed tension as well as in cAMP. The corresponding dose-response curves run parallel to each other but differed by about 1.5 log units whereby the developed tension was evoked by lower concentrations. Phentolamine (10−6 M) shifted the curve for the positive inotropic action by about 1.5 log units but did not affect that for increase in cAMP. Therefore, in the presence of the α-adrenolytic drug phentolamine the difference between both curves became smaller so that both curves were superimposed. Papaverine (10−5 M) shifted the whole curve for cAMP upwards and enhanced the maximal contractile response to phenylephrine mediated by stimulation of β-adrenoceptors. 5. The present results indicate that the positive inotropic action of phenylephrine in lower concentrations (〈10−5 M) induced by stimulation of α-adrenoceptors is independent of the level of cAMP. The positive inotropic action of the higher concentrations of phenylephrine induced via stimulation of β-adrenoceptors was preceded by an accumulation of cAMP; the inhibition of the cAMP phosphodiesterase activity by papaverine enhanced the actions of phenylephrine both on the level of cAMP and on the contractile force.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1912
    Keywords: Dopamine ; Contractility ; Papillary muscle ; α- and β-adrenoceptors ; Cyclic AMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the isolated rabbit papillary muscle the effects of dopamine on the contractile force and on the level of 3′,5′-cyclic adenosine monophosphate (cAMP) at different frequencies of stimulation were studied and compared with those of isoprenaline and adrenaline. 1. When the frequency of stimulation was increased from 0.5–2.5 Hz the dose-response curves for the positive inotropic effect of dopamine as well as of isoprenaline were shifted to the left, whereas the maximum of the developed tension reached for both drugs remained unchanged. 2. At a frequency of stimulation of 0.5 Hz pindolol (3×10−8 M) and phentolamine (10−6 M), respectively, did not affect the dose-response curve for dopamine; only the simultaneous administration of pindolol plus phentolamine shifted the dose-response curve to the right. In the presence of cocaine (3×10−5 M) as well as in that of cocaine plus corticosterone (4×10−5 M) the dose-response curve for dopamine was shifted to the right. On the other hand, the upper part of the dose-response curve for adrenaline was shifted to the right by pindolol (3×10−8 M), the lower part by phentolamine (10−6 M) and the whole curve by the application of both antagonists. 3. At a frequency of stimulation of 2.5 Hz neither pindolol (3×10−8 M) nor phetolamine (10−6 M) influenced the dose-response curve for dopamine, whereas the simultaneous administration of both drugs shifted the whole curve to the right. 4. Dopamine (10−4 M) increased significantly the content of the cAMP after 60 s by about 40% (at 0.5 Hz) and 50% (at 1.0 Hz), respectively, but this increase was by far less compared with that obtained by isoprenaline (3×10−7 M). 5. Pindolol (3×10−8 M) completely abolished the increase of the cAMP-content evoked by dopamine (10−4 M), while phentolamine (10−6 M) enhanced the elevation of the cAMP-level to nearly the same extent as isoprenaline (3×10−7 M) did. 6. The increase of the cAMP level induced by adrenaline (10−5 M) was comparable with that caused by isoprenaline (3×10−7 M). While phentolamine (10−6 M) did not influence the adrenaline induced increase of the cAMP content, pindolol completely abolished it. 7. The present results are compatible with the view, that the positive inotropic effect via stimulation of β-adrenoceptors is mediated by cAMP, while that of α-adrenoceptors is not. Furthermore it is concluded, that dopamine produces its positive inotropic effect by a cAMP-dependent direct and/or indirect β-adrenoceptor stimulation as well as by a cAMP-independent direct α-adrenoceptor stimulation to about the same degree.
    Type of Medium: Electronic Resource
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