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  • 1975-1979  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 6 (1979), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Effects of epinine on cyclic AMP and contractility were investigated in rabbit papillary muscles driven at a rate of 0.5 or 2.0 Hz.2. When the frequency of stimulation was increased from 0.5 to 2.0 Hz, the log dose-response curve for the positive inotropic effect of epinine was displaced to the left, whereas the maximum of the developed tension was not changed.3. At both frequencies phentolamine (1 μmol/1) shifted the lower part of the log dose-response curve for epinine to the right, whereas pindolol (30 nmol/1) affected mainly the upper part. In the presence of both a- and β-adrenoceptor antagonists, the whole curve was shifted to the right in a parallel manner. However, cocaine (30 μmol/1) did not significantly influence the log dose-response curve of epinine.4. At 0.5 Hz a submaximal effective concentration of epinine (100 μmol/1) led to an approximately 100% increase of the cyclic AMP level after 60 s; the same increase of the cyclic AMP level was induced at 2.0 Hz by one-third the concentration of epinine (30 μmol/1).5. Phentolamine (1 μmol/1) did not affect the increase of the cyclic AMP level evoked by epinine, whereas pindolol (30 μmol/1) completely depressed it.6. The present results indicate that epinine produces its positive inotropic effect through direct stimulation of myocardial α-adrenoceptors as well as β-adrenoceptors, depending upon the concentration: in lower concentrations it acts mainly on α-adrenoceptors, whereas in higher concentrations it acts predominantly on β-adrenoceptors. The positive inotropic effect through α-adrenoceptor stimulation is mediated by cyclic AMP, while that through a-adrenoceptors is not.
    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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