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

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 1990, Vol.341 (1-2), p.14-21
• Main Authors: DEIGHTON, N. M, MOTOMURA, S, BORQUEZ, D, ZERBOWSKI, H.-R, DOETSCH, N, BRODDE, O.-E
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Carbachol - pharmacology; Electric Stimulation; Fundamental and applied biological sciences. Psychology; Heart; 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; Vertebrates: cardiovascular system
• ISSN: 0028-1298; 1432-1912
• 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.