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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: 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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