caa a22 4500 469079010 CHVBK 20180323132944.0 cr unu---uuuuu 170328e19920101xx s 000 0 eng 10.1007/BF00175462 doi (NATIONALLICENCE)springer-10.1007/BF00175462 Binding characteristics and functional G protein coupling of muscarinic acetylcholine receptors in rat duodenum smooth muscle membranes [Elektronische Daten] [Claus Liebmann, Steffen Nawrath, Martin Schnittler, Harald Schubert, Karl-H. Jakobs] Summary: The non-selective labelled antagonist [3H]N-methyl-scopolamine ([3H]NMS) was used to identify muscarinic acetylcholine receptors in rat duodenum smooth muscle membranes. Saturation and kinetic experiments revealed a binding site with a KD-value of 0.2-0.3 nmol/l and a receptor concentration (Bmax) of 100 fmol/mg protein. The affinities of eight selective muscarinic antagonists were determined and compared with those at M1 (rat cerebral cortex), M2 (rat heart), M3 (rat submandibular gland) and M4 (data from Dörje et al. 1991) receptors. The "M2-selective” agent AF-DX 116, the group of "M2/M4-selective” compounds himbacine, AF-DX 384, AQ-RA 741 and methoctramine but also the "M3-selective” HHSiD showed affinities corresponding to M2 and/or M4 sites. The intermediate affinity of 4-DAMP favours a mixed M2/M4 receptor population mainly containing M2 receptors. Two compounds, pirenzepine and AQ-RA 741, displayed biphasic displacement curves indicating the presence of a small population of putative M1 receptors. The rat duodenum antagonist binding profile, however, is not consistent with the presence of M3 receptors. We further demonstrate a concentration-dependent stimulation of [35S]GTP[S] binding to duodenal G proteins by the muscarinic agonist oxotremorine. Estimation of the binding parameters of GTP[S] in absence and presence of oxotremorine provided evidence for a catalytic activation of G proteins by agonist-activated muscarinic receptors in rat duodenal membranes and a strong signal amplification on the G protein level. Springer-Verlag, 1992 Rat duodenum nationallicence Muscarinic receptors nationallicence M2/M4/M1 subtypes nationallicence Catalytic G protein activation nationallicence Liebmann Claus Institut für Biochemie and Biophysik, Biologische Fakultät, Friedrich-Schiller-Universität Jena, Philosophenweg 12, 0-6900, Jena, Federal Republic of Germany aut Nawrath Steffen Institut für Biochemie and Biophysik, Biologische Fakultät, Friedrich-Schiller-Universität Jena, Philosophenweg 12, 0-6900, Jena, Federal Republic of Germany aut Schnittler Martin Institut für Biochemie and Biophysik, Biologische Fakultät, Friedrich-Schiller-Universität Jena, Philosophenweg 12, 0-6900, Jena, Federal Republic of Germany aut Schubert Harald Tierexperimentelles Zentrum der Medizinischen Fakultat, Friedrich-Schiller-Universitat Jena, O-6900, Jena, Federal Republic of Germany aut Jakobs Karl-H Pharmakologisches Institut der Universitat Essen, W-4300, Essen, Federal Republic of Germany aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/1(1992-01-01), 7-15 0028-1298 345:1<7 1992 345 210 https://doi.org/10.1007/BF00175462 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00175462 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Liebmann Claus Institut für Biochemie and Biophysik, Biologische Fakultät, Friedrich-Schiller-Universität Jena, Philosophenweg 12, 0-6900, Jena, Federal Republic of Germany aut NATIONALLICENCE 700 1- Nawrath Steffen Institut für Biochemie and Biophysik, Biologische Fakultät, Friedrich-Schiller-Universität Jena, Philosophenweg 12, 0-6900, Jena, Federal Republic of Germany aut NATIONALLICENCE 700 1- Schnittler Martin Institut für Biochemie and Biophysik, Biologische Fakultät, Friedrich-Schiller-Universität Jena, Philosophenweg 12, 0-6900, Jena, Federal Republic of Germany aut NATIONALLICENCE 700 1- Schubert Harald Tierexperimentelles Zentrum der Medizinischen Fakultat, Friedrich-Schiller-Universitat Jena, O-6900, Jena, Federal Republic of Germany aut NATIONALLICENCE 700 1- Jakobs Karl-H Pharmakologisches Institut der Universitat Essen, W-4300, Essen, Federal Republic of Germany aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/1(1992-01-01), 7-15 0028-1298 345:1<7 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer