Endogenous Inhibitor of Ligand Binding to the Muscarinic Acetylcholine Receptor

R. Diaz-Arrastia, T. Ashizawa, S. H. Appel

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


An endogenous inhibitor of L-[3H]quinuclinidinyl benzilate binding to the brain muscarinic acetylcholine receptor was identified. [3H}Quinuclinidinyl benzilate binding to rat brain synaptosomes was measured using a filtration assay. The inhibitor was prepared from several calf tissues and was found in highest specific activity in thymus. The loss of binding activity was slow, requiring a 30-40 min preincubation of the synaptosomes with the inhibitor, and reversed by removing the inhibitor by washing the membranes. Scatchard analysis of the binding data showed that the inhibition was noncompetitive resulting from both a decrease in affinity and a decrease in the number of binding sites. Zn2+ was required in low concentrations for this effect. Muscarinic acetylcholine receptor in synaptic membranes and in membranes free of most peripheral membrane proteins was still sensitive to inhibition. Preliminary characterization of the inhibitory molecule showed that it is of low molecular weight, moderately heat-stable, and acidic. The inhibitor was inactivated by reagents that are nonspecific for nucleophiles, but not by reagents specific for primary amine or thiol groups.

Original languageEnglish (US)
Pages (from-to)622-628
Number of pages7
JournalJournal of Neurochemistry
Issue number2
StatePublished - Jan 1 1985


  • Modulators
  • Muscarinic acetylcholine receptors

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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