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  • 1
    ISSN: 1432-1912
    Keywords: Adenosine ; Phenylisopropyladenosine ; Negative inotropic effect ; Cyclic AMP ; Ventricular myocardium of the dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experiments were carried out to characterize the adenosine-induced negative inotropic effect in relation to the extent of β-adrenoceptor activation in the isolated dog left ventricular myocardium. Adenosine and R-N6-phenylisopropyladenosine inhibited the positive inotropic effect of isoprenaline (10−7 mol/1 and lower) about 20% of its maximal response, which was antagonized by an A1 adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine in a concentration-dependent manner. The negative inotropic effect of adenosine disappeared and that of R-N6-phenylisopro-pyl-adenosine decreased when the isoprenaline concentration was elevated to the level higher than 10−7 mol/1. Adenosine deaminase (1.5 U/ml) that abolished the negative inotropic effect of adenosine enhanced the effect of R-N6-phenylisopropyladenosine, indicating that endogenous adenosine released by high isoprenaline concentration (10−6 mol/1) modulates the interaction. The maximal response to adenosine and R-N6-phenylisopro-pyladenosine determined in the presence of 10−7 mol/1 isoprenaline was 50% of that of carbachol which elicited the maximal inhibition even in the presence of 10−6 mol/1 isoprenaline. The negative inotropic effects of R-N6-phenylisopropyladenosine and carbachol were additive to the maximal response equivalent to that of carbachol. The difference in the efficiency between the adenosine and muscarinic receptor agonists may be partly ascribed to the difference in densities of the respective receptors in the dog ventricular myocardium. The negative inotropic effect of R-N6-phenylisopropyladenosine in the presence of isoprenaline was associated with decrease in cyclic AMP levels elevated previously by isoprenaline. The elevation of cyclic AMP levels caused by isoprenaline (3 × 10−7 mol/1) was abolished by R-N6-phenylisopro-pyladenosine (10−4 mol/1), while the contractile response was reduced only by 30% with R-N6-phenylisopro-pyladenosine. In the absence of β-adrenoceptor stimulation R-N6-phenylisopropyladenosine elicited a negative inotropic effect without changes in cyclic AMP levels, but this effect was less than 10% of the basal force of contraction. It is concluded that in the dog ventricular myocardium adenosine receptors play a role for the inhibitory regulation of contractility, which is influenced markedly by the pre-existing level of β-adrenoceptor activation.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 339 (1989), S. 362-366 
    ISSN: 1432-1912
    Keywords: α-Adrenoceptors ; β-Adrenoceptors ; Positive isotropic effect ; Phenylephrine ; Ferret ventricular myocardium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary [3H]prazosin bound to the membrane fraction derived from the ferret ventricular muscle with high affinity in a saturable manner (K d = 0.25 nmol/l and B max = 27 fmol/mg protein in the right ventricle). [3H]CGP-12177, a β-adrenoceptor ligand, bound to the membrane fraction with a K d value of 0.29 nmol/l and a B max of 42 fmol/mg protein. In the isolated ferret papillary muscle driven at 1 Hz at 37°C, phenylephrine elicited a concentration-dependent positive intropic effect. The maximal effect of phenylephrine was comparable to that of isoprenaline. Prazosin (0.3 μol/l) shifted the concentration-response curve for phenylephrine slightly but significantly to the right, the maximal response being unaffected. In contrast, bupranolol (0.3 gmol/l) shifted the curve for phenylephrine markedly downwards: the maximal response was depressed significantly to 40% and the curve became less steep. In the presence of prazosin and bupranolol the curve was shifted to the right, being essentially parallel to the control curve. These results indicate that in the ferret ventricular myocardium both α- and β-adrenoceptors mediate the positive inotropic effect of phenylephrine. The extent of contribution of the two classes of adrenoceptor is quite different from that in other mammalian species. In the ferret heart, β-adrenoceptors predominate over α-adrenoceptors in mediating the positive inotropic effect of phenylephrine, although the number of β-adrenoceptors is not especially high when compared with other species.
    Type of Medium: Electronic Resource
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