Chapter 4. Molecular/Cell Biology of G-Protein Coupled CNS Receptors

Abstract

Publisher Summary Recent advances in the molecular and cell biology have supplemented classical pharmacological studies to provide a more precise understanding of the diversity, localization, nature, and function of G-protein coupled receptor (GPCR). In support of drug design efforts, the preparation of heterologous expression systems containing individual cloned GPCRs in mammalian cell lines can yield very precise biological assays for structure activity relationship (SAR) studies. The GPCR superfamily contains well over 100 receptor proteins that play crucial roles in the regulation of numerous physiological processes in the central and peripheral nervous systems. Although the precise molecular structures of GPCRs are not known, because these membrane-bound proteins have not yielded to crystallization and x-ray diffraction studies, they appear to be similar in structure to the membrane protein bacteriorhodopsin that has been studied by electron diffraction: seven helical transmembrane (7-TM) domains that are flanked by an extracellular N-terminus and an intracellular C-terminus. This structural motif is supported by a number of biophysical, biochemical, and molecular biological studies on various GPCRs. The chapter discusses various roles of adenosine receptors, cannabinoid receptors, dopamine receptors, metabotropic glutamate receptors, and serotonine receptors. In terms of diversity of the central nervous system (CNS) receptors, serotonin has no peers: far more 5-HT subtypes have been identified than any other CNS receptors of the GPCR class. This structural diversity has caused considerable confusion regarding the nomenclature of 5-HT receptors. Information about receptor structure and diversity, tissue distribution and functional coupling of receptors to effectors is available because of the tremendous scientific advances that have occurred in the molecular biology of GPCRs.