Muscarinic cholinoceptors in the human heart: demonstration, subclassification, and distribution

Naunyn Schmiedebergs Arch Pharmacol. 1990 Jan-Feb;341(1-2):14-21. doi: 10.1007/BF00195052.


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 greater than AF-DX 116 greater than hexahydrosiladifenidol (HHSiD) greater than pirenzepine. (3) On isolated electrically driven right atrial and left papillary muscle preparations (with force of contraction enhanced by 10(-5) mol/l isoprenaline), carbachol (10(-8)-10(-4) mol/l) caused concentration-dependent decreases in force of contraction; the pD2-value for carbachol was 6.65 +/- 0.09 (n = 8, atria) and 6.62 +/- 0.08 (n = 10, papillary muscles). In both tissues M-cholinoceptor antagonists antagonized the negative inotropic effect of carbachol with an order of potency: atropine greater than AF-DX 116 greater than HHSiD greater than pirenzepine, identical to that obtained in radioligand binding experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbachol / pharmacology
  • Electric Stimulation
  • Heart / drug effects
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Membranes / drug effects
  • Membranes / metabolism
  • Myocardial Contraction / drug effects
  • Myocardium / metabolism*
  • N-Methylscopolamine
  • Papillary Muscles / drug effects
  • Papillary Muscles / metabolism
  • Piperidines / pharmacology
  • Pirenzepine / analogs & derivatives
  • Pirenzepine / pharmacology
  • Radioligand Assay
  • Receptors, Muscarinic / metabolism*
  • Scopolamine Derivatives


  • Piperidines
  • Receptors, Muscarinic
  • Scopolamine Derivatives
  • Pirenzepine
  • Carbachol
  • hexahydrosiladifenidol
  • otenzepad
  • N-Methylscopolamine