Characterization of Receptors Based on Receptor-Mediated Responses

Summary

The methods summarized in this chapter provide approaches for characterizing the specificity of a drug or hormone effect. This specificity provides evidence for a receptor-mediated response. Once a receptor is implicated in a response, a variety of analyses are available for estimating the equilibrium dissociation constants for agonists, partial agonists, antagonists and inverse agonists. It is clear that evaluation of receptor-mediated response provides a great deal of information, both qualitatively and quantitatively, regarding ligand-receptor interactions and subsequent receptor-activated responses. These approaches were developed when the biological preparation under study was intact tissue or native target cells. However, in current high throughput screening technologies where the read-out is a cell-based response, these strategies have comparable value in elucidating the mechanism and providing quantitative parameters to describe the properties of novel agents. In fact, the only receptor parameter that cannot be obtained from studies of dose-response relationships in intact cell or tissue preparations is receptor density. Radioligand binding methods for characterization of receptors yielding information concerning receptor specificity, affinity and density are discussed in chapter 3.