Agonist efficiency from concentration-response curves: Structural implications and applications.

ABSTRACT: Agonists are evaluated by a concentration-response curve (CRC), with a midpoint (EC₅₀) that indicates potency, a high-concentration asymptote that indicates efficacy, and a low-concentration asymptote that indicates constitutive activity. A third agonist attribute, efficiency (η), is the fraction of binding energy that is applied to the conformational change that activates the receptor. We show that η can be calculated from EC₅₀ and the asymptotes of a CRC derived from either single-channel or whole-cell responses. For 20 agonists of skeletal muscle nicotinic receptors, the distribution of η-values is bimodal with population means at 51% (including acetylcholine, nornicotine, and dimethylphenylpiperazinium) and 40% (including epibatidine, varenicline, and cytisine). T

SUBMITTER: Indurthi DC 

PROVIDER: S-EPMC8204218 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature