Differential Allosteric Effects of 8-(n,n-Diethylamine) Octyl-3,4,5-Trimethoxybenzoate-HC1(TMB-8) on Muscarinic Receptor Subtypes.

摘要

TMB-8, a putative inhibitor of intracellular calcium mobilization, prevents the binding of the muscarinic ligand (3H)N-methylscopolamine. The inhibition was observed in four tissues from guinea pig; cortex, heart, pancreas, and ileum, representing M1, cardiac M2, glandular M2, and heterogeneous M2 subtypes of muscarinic receptors, respectively. The Ki values for all four tissues were approximately 4 micrometers. However, dissociation kinetics revealed that TMB-8 interacted with an allosteric site of three muscarinic receptor subtypes but not the subtype from the pancreas. These results indicate that TMB-8 interacts with muscarinic receptors, and therefore would disrupt calcium mobilization or any second messenger system coupled to these receptors. Keywords: Reprints; Muscarinic receptor subtypes; Dissociation kinetics; Allosteric site; TMB-8; Radioligand assay; Molecular models. (aw)