Anomalous binding of [³H]N-methylscopolamine to rat brain muscarinic receptors

In the present studies, we investigate the binding properties of [³H]quinuclidinyl benzilate ([³H]QNB) and [³H]N-methylscopolamine ([³H]NMS) to muscarinic acetylcholine receptors (mAChR) in rat brain homogenates. Our results indicate that the hydrophilic receptor ligand, [³H]NMS, is able to interact with high affinity only with a fraction of the receptor sites available to the lipophilic ligand, [³H]QNB. Furthermore, displacement experiments demonstrated that while both unlabeled QNB and NMS displaced [³H]NMS binding according to the law of mass-action, NMS, but not QNB, displayed binding heterogeneity when [³H]QNB was used as a ligand. Our data suggest that the lipid solubility of a particular mAChR ligand might play an important role in determining its profile of binding to the receptor.