The Mechanism of Inverse Agonists Binding to G-Protein Coupled Receptors, Histamine Receptor H1 and Histamine Receptor H2

Abstract

The thesis discusses the mechanism of an inverse agonist binding to receptors and how it is different from an agonist binding to the same receptor. The specific receptors that were focused on were histamine receptor H1 (HRH1) and histamine receptor H2 (HRH2) which are types of G-protein coupled receptors (GPCR). It is understood how an agonist binds to a GPCR and activates a signaling pathway within the cell, and that an inverse agonist can bind to the same receptor but elicit an opposite response. The current idea behind the mechanism of an inverse agonist is that it binds to the receptor, and the G-protein is not being recruited to continue the signaling pathway within the cell. The hypothesis was that the G-protein is recruited when the inverse agonist binds to the GPCR, but the G-protein would be in its GDP state or its inactivated state. To test the hypothesis, a luciferase assay was done in different conditions where the bioluminescence absorbance was measured and recorded to see if there was protein-protein activity between the GPCR and the G-protein. From doing multiple trials, it is still believed that the G-protein is not being recruited to elicit the signaling pathway when an inverse agonist binds to the receptors.