Anomalous binding of [3H]N-methylscopolamine to rat brain muscarinic receptors.
In the present studies, we investigated 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.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D019832:N-Methylscopolamine; D011813:Quinuclidinyl Benzilate; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000378:metabolism*
D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D011813:Quinuclidinyl Benzilate; D019832:N-Methylscopolamine