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 = 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.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000403:Airway Resistance / Q000187:drug effects; D001570:Benzodiazepinones / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D002648:Child; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000378:metabolism / Q000494:pharmacology; D008875:Middle Aged; D009116:Muscarine / Q000031:analogs & derivatives / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects*; D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D014132:Trachea / Q000294:innervation* / Q000378:metabolism
D001570:Benzodiazepinones; D008688:Methacholine Compounds; D011976:Receptors, Muscarinic; D016210:Methacholine Chloride; C008446:5-methylfurtrethonium; D006165:Guanylyl Imidodiphosphate; D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate; D009116:Muscarine