Studies on muscarinic acetylcholine receptors from mouse brain: Characterization of the interaction with antagonists

The binding of tritium labeled N-methyl-4-piperidyl benzilate (4-NMPB) and scopolamine to the muscarinic receptor from mouse brain was investigated at 10, 25 and 37 °C. Approach to equilibrium experiments indicated that association involved a single population of binding sites. The formation of at least two types of ligand-receptor complexes had however to be assumed to explain the data obtained at 25 and 37 °C by equilibrium and dissociation experiments. In contradistinction, at 10 °C a single population of ligand-receptor complexes could be detected. The simplest model which fits the experimental findings consists of a fast binding step followed by a slow isomerization process of the receptor-ligand complex.