[3H]N-methylscopolamine dissociation from muscarine receptors affected by low concentrations of allosteric modulators

Abstract

The ability of allosteric ligands to modulate the dissociation rate of [³H]N-methylscopolamine from atrial muscarinic receptors in the presence of varying concentrations of unlabelled N-methylscopolamine or atropine was evaluated. Gallamine, at a concentration approximating its K_D value, slowed the dissociation of [³H] N-methylscopolamine in the presence of ca. 30× K_D of both unlabelled NMS or atropine. This was less evident when concentrations of ca. 1000× K_D of the unlabelled antagonists were employed. Similar findings were made with another allosteric modulator. These results indicate that gallamine can act allosterically at low concentrations.