[3H]N-methylscopolamine dissociation from muscarine receptors affected by low concentrations of allosteric modulators.
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 KD value, slowed the dissociation of [3H]N-methylscopolamine in the presence of ca. 30 x KD of both unlabelled NMS or atropine. This was less evident when concentrations of ca. 1000 x KD 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.
Christopoulos
A
A
Department of Pharmacology, Victorian College of Pharmacy (Monash University), Parkville, Australia.
Mitchelson
F
F
D000494:Allosteric Regulation; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D005703:Gallamine Triethiodide / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D018727:Muscarinic Antagonists / Q000494:pharmacology; D019832:N-Methylscopolamine; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010276:Parasympatholytics / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000378:metabolism*
D008024:Ligands; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D001285:Atropine; D005703:Gallamine Triethiodide; D019832:N-Methylscopolamine