OR8B4 Activators

OR8B4 include a variety of compounds commonly found in fragrant plants and used in flavorings and perfumery. These molecules, such as citronellal, eugenol, geraniol, methyl salicylate, β-ionone, phenethyl alcohol, limonene, benzaldehyde, hexanal, α-pinene, linalool, and isoamyl acetate, are known to interact with and activate olfactory receptors. When these chemicals bind to OR8B4, a signaling cascade is initiated. This cascade begins with the replacement of GDP with GTP on the G-protein coupled to the receptor, leading to the activation of adenylate cyclase, which then increases the levels of cAMP within the cell. This increase in cAMP can activate various downstream signaling pathways, ultimately leading to cellular responses that translate into the perception of smell.

Each of these ligands can bind to OR8B4 at its specific binding site, which is typically tuned to the molecular shape and functional groups of the odorant molecule. Upon binding, a conformational change occurs in OR8B4 that triggers the associated G-protein to exchange GDP for GTP, activating it. The activated G-protein then dissociates into subunits which interact with adenylate cyclase, catalyzing the conversion of ATP to cAMP. The rise in cAMP opens ion channels, particularly calcium channels, leading to an influx of calcium ions. This ion exchange generates an electrical signal which propagates along the olfactory neurons and is eventually processed in the brain as a distinct odor. The process is terminated when the GTP on the G-protein is hydrolyzed to GDP, returning the G-protein to its inactive state, and the cAMP levels are reduced by phosphodiesterases, which helps reset the receptor for another activation event.