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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 341 (1990), S. 14-21 
    ISSN: 1432-1912
    Keywords: Human cardiac muscarinic cholinoceptors ; Muscarinic cholinoceptor subtypes ; Human right atrium ; Human left papillary muscle ; Negative inotropic effect ; [N-Methyl-3H]-scopolamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In human atrial and ventricular myocardium, the muscarinic cholinoceptor (M-cholinoceptor) populations were characterized by means of radioligand binding (with [N-methyl-3H]-scopolamine ([3H]-NMS) as the ligand) and functional experiments (negative inotropic effect of carbachol on isolated electrically driven right atrial and left papillary muscle preparations). (1) Binding of [3H]-NMS to human atrial and ventricular membranes was rapid, reversible and saturable (KD-values: 0.5–1.0 nmol/l). The maximal number of [3H]-NMS binding sites, however, was approximately 2.5-fold higher in right and left atrial membranes (200–250 fmol[3H]-NMS specifically bound/mg protein) than in right and left ventricular membranes (80–100 fmol/mg protein). (2) M-cholinoceptor antagonists inhibited [3H]-NMS binding to right atrial and left ventricular membranes with steep, monophasic competition curves indicating interaction with a single class of binding sites. In both tissues the order of potency was: atropine 〉 AF-DX 116 〉 hexahydro-siladifenidol (HHSiD) 〉 pirenzepine. (4) It is concluded that, in the human heart, functional M-cholinoceptors mediating negative inotropic effects exist that belong predominantly (if not exclusively) to the M2-subtype. However, the atrial regions of the human heart are more densely endowed with these M2-cholinoceptors than the ventricular myocardium.
    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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