Second M₃ muscarinic receptor binding site contributes to bronchoprotection by tiotropium.

ABSTRACT:

Background and purpose

The bronchodilator tiotropium binds not only to its main binding site on the M₃ muscarinic receptor but also to an allosteric site. Here, we have investigated the functional relevance of this allosteric binding and the potential contribution of this behaviour to interactions with long-acting β-adrenoceptor agonists, as combination therapy with anticholinergic agents and β-adrenoceptor agonists improves lung function in chronic obstructive pulmonary disease.

Experimental approach

ACh, tiotropium, and atropine binding to M₃ receptors were modelled using molecular dynamics simulations. Contractions of bovine and human tracheal smooth muscle strips were studied.

Key results

Molecular dynamics simulation revealed extracellular v

SUBMITTER: Kistemaker LEM 

PROVIDER: S-EPMC6637226 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature