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  • Adenosine  (3)
  • Negative inotropic effect  (2)
  • Papillary muscle  (2)
  • 1
    ISSN: 1432-1912
    Schlagwort(e): Adenosine ; Phenylisopropyladenosine ; Negative inotropic effect ; Cyclic AMP ; Ventricular myocardium of the dog
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-1912
    Schlagwort(e): Adenosine ; Phenylisopropyladenosine ; Adenosine receptors ; Negative inotropic effect ; G proteins ; Ferret ventricular myocardium
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary An adenosine A1 receptor agonist R-N6-phenylisopropyladenosine (R-PIA) elicited a pronounced negative inotropic effect with the EC50 value of 0.69 μmol/1 in the presence of a β-adrenoceptor blocking agent bupranolol (0.3 μmol/1) in the isolated ferret papillary muscle. The negative inotropic effect of R-PIA was not associated with changes in cyclic AMP level. Adenosine and other A1 receptor agonists also elicited a negative inotropic effect. DPCPX (1,3-dipropyl-8-cyclopentyl xanthine) antagonized the negative inotropic effect of R-PIA in a competitive manner (pA2 value = 8.4). The inhibitory action of R-PIA was markedly attenuated in the ventricular muscle preparation isolated from ferrets pretreated with pertussis toxin that caused ADP-ribosylation of 39 kDa proteins in the membrane fraction. In the membrane fraction derived from the ferret ventricle, [3H]-DPCPX bound to a single binding site in a saturable and reversible manner with high affinity (Kd value = 1.21±0.41 nmol/l; B max = 12.8±3.02 fmol/mg protein; n = 7). The binding characteristics of [3H]-DPCPX in the rat ventricle (Kd value = 1.51 ±0.09 nmol/l; B max = 12.7±1.47 fmol/mg protein; n = 5) were similar to those in the ferret. On the other hand, the content of Go, a major pertussis toxin-sensitive G protein in the ferret heart, was much higher in the ferret than in the rat ventricle. The present results indicate that adenosine receptors may play an important role in the inhibitory regulation of ventricular contractility in the ferret in contrast to other mammalian species. The signal transduction process subsequent to agonist binding to A1 receptors including the pertussis toxin-sensitive G protein and ion channels may be responsible for the unique inhibitory action of adenosine in this species.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1432-1912
    Schlagwort(e): Dopamine ; Contractility ; Papillary muscle ; α- and β-adrenoceptors ; Cyclic AMP
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 302 (1978), S. 235-238 
    ISSN: 1432-1912
    Schlagwort(e): Nifedipine ; Verapamil ; Calcium ; Ventricular automaticity ; Papillary muscle
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In isolated, blood-perfused canine papillary muscles intra-arterial injection of calcium-antagonistic coronary vasodilators, nifedipine and verapamil, produced a dose-related decrease in force of contraction. The ventricular rate of about 40 beats/min was not significantly changed by nifedipine even in doses which profoundly decreased the force of contraction. Verapamil changed the ventricular rate in a biphasic manner, but the changes remained as small as about 10% of the basal rate in doses which markedly suppressed the force of contration. Calcium chloride elicited an increase in force of contraction but depressed automaticity. The present results show that in response to nifedipine, verapamil and calcium ions, ventricular automaticity has characteristics different from those of the sinus node.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 351 (1995), S. 610-617 
    ISSN: 1432-1912
    Schlagwort(e): Ferret ; Ventricular myocytes ; Acetylcholine ; Adenosine ; Muscarinic K+ ; channel ; G protein
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The properties of the K+ channel activated by acetylcholine (ACh) and adenosine (Ado) were examined in single ferret ventricular myocytes using patch-clamp techniques. In the whole-cell configuration, ACh and Ado induced an inwardly rectifying K+ current and shortened the action potential duration. The effect of ACh was blocked by atropine, while the Ado effect was interrupted by 8-cyclopenty1,1,2-dipropyl xanthine, a specific Ado A1 receptor antagonist. In cell-attached recordings, ACh and Ado added to the pipette solution activated a single population of inwardly rectifying K+ channels, distinct from the i K1 channel. The channel had a slope conductance of ∼ 40 pS in symmetrical 150 mM K+ solutions and a mean open time of 0.8 ms. Excision of the patch into the inside-out patch configuration in guanosine triphosphate (GTP)-free solution abolished the channel activity. The channel was reversibly reactivated by adding GTP to the intracellular side of the patch. GTPγS activated the channel irreversibly. When the inside-out patch was treated with the A protomer of pertussis toxin (PTX), intracellular GTP no longer activated the K+ channel. The results show that ferret ventricular myocytes possess a K+ channel activated by both muscarinic and Ado A1 receptors. Its electrophysiological properties and the gating by a PTX-sensitive G protein in a membrane-delimited fashion are identical with those of the muscarinic K+ channels in nodal and atrial tissues of other species. In conclusion, the G protein-gated muscarinic K+ channel is expressed in ferret ventricular myocardium and may underlie the direct negative inotropism of ACh and Ado in this tissue.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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