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).
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(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).
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(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.
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(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.
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Deighton, N.M., Motomura, S., Borquez, D. et al. Muscarinic cholinoceptors in the human heart: demonstration, subclassification, and distribution. Naunyn-Schmiedeberg's Arch Pharmacol 341, 14–21 (1990). https://doi.org/10.1007/BF00195052
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DOI: https://doi.org/10.1007/BF00195052