Histamine H2 Receptor Biased Signaling Methods

Abstract

Advances in the study of G protein-coupled receptors (GPCRs) allow understanding of the existence of multiple possible receptor conformational states. Among the wide range of possible events that could be mediated by a receptor (second messenger modulation, dimerization, desensitization, internalization, G protein-dependent signaling, gene regulation, etc), the ligand–receptor complex governs the ultimate downstream signaling event and the final cellular response. To analyze the pluridimensional aspect of ligand efficacy, there is a need to employ a wide range of experimental tools that enable the study of receptor behaviors. In an attempt to contribute to the study and comprehension of the biased behavior of histamine H2 receptor (H2R) ligands, the aim of this chapter is to provide experimental tools that facilitate the exploration and analysis of the pluridimensional nature of H2R ligands. We hope that in the future it would be possible to develop ligands that take advantage of biased signaling by selectively activating the beneficial signaling events of the H2R and blocking the undesired ones.