Characterization of the muscarinic receptor in human tracheal smooth muscle

• Published in: Naunyn-Schmiedeberg's archives of pharmacology Vol. 331; no. 2-3; p. 247
• Main Authors: van Koppen, C J, Rodrigues de Miranda, J F, Beld, A J, Hermanussen, M W, Lammers, J W, van Ginneken, C A
• Format: Journal Article
• Language: English
• Published: Germany 01.11.1985
• Subjects: Adolescent; Adult; Aged; Airway Resistance - drug effects; Benzodiazepinones - metabolism; Benzodiazepinones - pharmacology; Binding, Competitive; Child; Guanylyl Imidodiphosphate - pharmacology; Humans; In Vitro Techniques; Kinetics; Methacholine Chloride; Methacholine Compounds - metabolism; Methacholine Compounds - pharmacology; Middle Aged; Muscarine - analogs & derivatives; Muscarine - metabolism; Muscle, Smooth - drug effects; Pirenzepine; Quinuclidinyl Benzilate - metabolism; Receptors, Muscarinic - drug effects; Receptors, Muscarinic - metabolism; Trachea - innervation; Trachea - metabolism
• ISSN: 0028-1298
• DOI: 10.1007/BF00634245

Muscarinic receptors in human tracheal smooth muscle were characterized by radioligand binding and functional studies. Specific [3H]-(-)-quinuclidinylbenzilate ([3H]-(-)-QNB) binding to tracheal smooth muscle membranes was reversible, stereoselective and of high affinity (Kd = 47 +/- 4 pmol/l; RT = 920 +/- 120 fmol/g tissue). Inhibition of specific [3H]-(-)-QNB binding by the M-1 selective antagonist pirenzepine was found to occur at relative high concentrations classifying the muscarinic receptor population as belonging to the M-2 subclass. Inhibition of specific [3H]-(-)-QNB binding by muscarinic agonists revealed the presence of high and low affinity sites in nearly equal proportions. 5'-Guanylylimidodiphosphate converted high affinity sites into low affinity sites although its effect was minimal. Log dose-contraction curves of methacholine had Hill coefficients of 1.10 +/- 0.04 with pD2-values of 6.75 +/- 0.02. Inhibition of specific [3H]-(-)-QNB binding by methacholine, however, was best described by a two binding site model with pKi-values considerably lower. The difference between these affinity values points to the presence of substantial receptor reserve.