Differential allosteric effects of 8‐(N,N‐diethylamino)octyl‐3,4,5‐trimethoxybenzoate‐HCl (TMB‐8) on muscarinic receptor subtypes

FEBS Letters

Gordon, Richard K.¹  Chiang, Peter K.¹ 

[1] Department of Applied Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA

关键词: Muscarinic receptor subtype;    Allosteric site;    Diethylamino octyl-3;    4;    5-trimethoxybenzoate-HCl 8-N;    N-;    Radioligand assay;    Molecular model;    Dissociation kinetics;   

DOI  :  10.1016/0014-5793(89)81578-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

TMB-8, a putative inhibitor of intracellular calcium mobilization, prevents the binding of the muscarinic ligand N-[³H]methylscopolamine. The inhibition was observed in four tissues from guinea pig; cortex, heart, pancreas, and ileum, representing Ml, cardiac M2, glandular M2, and heterogeneous M2 subtypes of muscarinic receptors, respectively. The K _i values for all four tissues were approx. 4 μM. However, dissociation kinetics revealed that TMB-8 interacted with an allosteric site of three muscarinic receptor subtypes but not the subtype from 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.

【 授权许可】

Unknown