Molecular Properties and Regulation of G-Protein-Coupled Receptors

This chapter discusses the molecular properties and regulation of G-protein coupled receptors. For many hormones, neurotransmitters, and chemotactic factors, signal transduction is accomplished through the interaction of bioactive molecules (agonists), with cell surface receptors, that couple to one or more species of heterotrimeric guanine-nucleotide-binding regulatory proteins (G-proteins). Receptors that share this mechanism of signal transduction have been termed as G-protein coupled receptors (GPCRs). These receptors play a critical role in many physiological processes, and have been targets for drug intervention and therapy in a wide range of diseases. However, the receptor, the inactive G-protein complex composed of three subunits (α, β, and γ), and the inactive effector enzymes are all associated, with the plasma membrane. The binding of a hormone or neurotransmitter triggers the association of the G-protein complex, with the agonist-occupied receptor. Agonist occupation of a GPCR leads to the generation of one or more intracellular second messengers, as a consequence of the activation of one or more effector enzymes, such as adenylyl cyclase, phospholipases A, C, or D, phosphodiesterases, and ion channels in specialized cells. © 1994 Academic Press, Inc