Characterization of receptor agonists and antagonists using bioSens-All®

Receptor-targeting molecules are usually classified based on their overt biological activity and binding site. An agonist is a molecule that directly produces a biological response upon binding the orthosteric (i.e., “active”) site on its target receptor. Agonists can be sub-categorized as full, partial or inverse based on their relative efficacies (vs. the endogenous agonist) in stimulating a biological response. Conversely, an antagonist is a compound that lacks inherent biological activity but interferes with the actions of an agonist upon binding its target receptor’s orthosteric site. Antagonists can also display full or partial efficacy [2]. Compound classification influences therapeutic indication and provides a mode of therapeutic action. Misclassification and mischaracterization can therefore have significant repercussions. Importantly, compound classification (especially for G-protein coupled receptors) is becoming increasingly complex due to the observation that different ligands can engage different downstream effector pathways and that a given ligand can display different (sometimes reversed) pathway-specific efficacies (i.e., pluridimensional efficacy/biased agonism) [3]. With these emerging paradigms comes the need for novel sensitive technologies capable of assessing compound efficacies across numerous pathways.

In this application note, we show how, in a single experiment via single-well multiple compound addition, the bioSens-All® Gai1 activation biosensor was used to characterize human dopamine D2 receptor (hD2R) agonists and an antagonist. This procedure can be performed for multiple effector pathways in parallel with bioSens-All®  biosensors.