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Human gastric mucosa expresses glandular M3 subtype of muscarinic receptors

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Abstract

Five subtypes of muscarinic receptors have been distinguished by pharmacological and molecular biological methods. This report characterizes the muscarinic subtype present in human gastric mucosa by radioligand binding studies. The receptor density was 27 ±6 fmollmg protein and the tritiated ligand N-methylscopolamine had an affinity of (KD)0.39±0.08 nM (n=11). The M1 receptor selective antagonist pirenzepine and the M2 receptor selective ligand AF-DX 116 had low affinities of 148±32 nM (n=13) and 4043±1011 nM (n=3) KD,respectively. The glandular M3 antagonists hexahydrosiladifenidol and silahexocyclium had high affinities of KD 78±23 nM (n=5) and 5.6±1.8 nM (n=3). The agonist carbachol interacted with a single low-affinity site and binding was insensitive to modulation by guanine nucleotides. Antagonist and agonist binding studies thus showed an affinity profile typical of M3 receptors of the glandular type.

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Authors and Affiliations

  1. Medizinische Klinik II, Klinikum Großhadern, Universität München, FRG

    A. Pfeiffer MD, C. Hanack BA, R. Kopp MD, R. Tacke PhD, U. Moser PhD, E. Mutschler MD, PhD, G. Lambrecht PhD & M. Herawi MD

  2. Institut für Anorganische Chemie, Universität Karlsruhe, FRG

    A. Pfeiffer MD, C. Hanack BA, R. Kopp MD, R. Tacke PhD, U. Moser PhD, E. Mutschler MD, PhD, G. Lambrecht PhD & M. Herawi MD

  3. Pharmakologisches Institut für Naturwissenschaftler, Universität Frankfurt, FRG

    A. Pfeiffer MD, C. Hanack BA, R. Kopp MD, R. Tacke PhD, U. Moser PhD, E. Mutschler MD, PhD, G. Lambrecht PhD & M. Herawi MD

Authors
  1. A. Pfeiffer MD
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  2. C. Hanack BA
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  3. R. Kopp MD
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  4. R. Tacke PhD
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  6. E. Mutschler MD, PhD
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  7. G. Lambrecht PhD
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  8. M. Herawi MD
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Additional information

This work was supported by the Deutsche Forschungsgemeinschaft (Pf 164/3-4; Ta 75/5-1) and the Fonds der Chemischen Industrie (R.T., E.M., and G.L.).

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Pfeiffer, A., Hanack, C., Kopp, R. et al. Human gastric mucosa expresses glandular M3 subtype of muscarinic receptors. Digest Dis Sci 35, 1468–1472 (1990). https://doi.org/10.1007/BF01540563

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  • DOI: https://doi.org/10.1007/BF01540563

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