Characterization of the muscarinic receptor in human tracheal smooth muscle

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 =...

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Bibliographic Details
Published in:Naunyn-Schmiedeberg's archives of pharmacology 1985-11, Vol.331 (2-3), p.247-252
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: Article
Language:English
Subjects:
acetylcholine
Adolescent
Adult
Aged
Airway Resistance - drug effects
Benzodiazepinones - metabolism
Benzodiazepinones - pharmacology
Binding, Competitive
Child
Guanylyl Imidodiphosphate - pharmacology
Humans
In Vitro Techniques
Kinetics
man
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
smooth muscle
trachea
Trachea - innervation
Trachea - metabolism
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Summary: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.
ISSN:0028-1298
1432-1912
DOI:10.1007/BF00634245