Correction to "A Scale of Agonism and Allosteric Modulation for Assessment of Selectivity, Bias, and Receptor Mutation".

A System-independent Scale of Agonism and Allosteric Modulation for Assessment of Selectivity, Bias and Receptor Mutation

Prediction of functionally selective allosteric interactions at an M3 muscarinic acetylcholine receptor mutant using Saccharomyces cerevisiae.

Saccharomyces cerevisiae is a tractable yeast species for expression and coupling of heterologous G protein-coupled receptors with the endogenous pheromone response pathway. Although this platform has been used for ligand screening, no studies have probed its ability to predict novel pharmacology and functional selectivity of allosteric ligands. As a proof of concept, we expressed a rat M(3) mu...

Engineered Context-Sensitive Agonism: Tissue-Selective Drug Signaling through a G Protein-Coupled Receptor.

Drug discovery strives for selective ligands to achieve targeted modulation of tissue function. Here we introduce engineered context-sensitive agonism as a postreceptor mechanism for tissue-selective drug action through a G protein-coupled receptor. Acetylcholine M2-receptor activation is known to mediate, among other actions, potentially dangerous slowing of the heart rate. This unwanted side ...

Seven transmembrane receptors as shapeshifting proteins: the impact of allosteric modulation and functional selectivity on new drug discovery.

It is useful to consider seven transmembrane receptors (7TMRs) as disordered proteins able to allosterically respond to a number of binding partners. Considering 7TMRs as allosteric systems, affinity and efficacy can be thought of in terms of energy flow between a modulator, conduit (the receptor protein), and a number of guests. These guests can be other molecules, receptors, membrane-bound pr...

Role of the AMPA receptors of paragigantocellularis lateralis nucleus in the inflammatory pain modulation in male rat

Introduction: The 17β-estradiol acts as a neurosteroid in the brain and modulates nociception by binding to the estrogen receptors and also by allosteric interaction with other membrane-bound receptors like glutamate receptors. Paragigantocellularis lateralis nucleus (LPGi) is one of the important brain regions implicated in the pain modulation. So, this study was designed to evaluate the ...