The Roles of G-protein coupled receptors in health and disease conditions
Authors: AO Ibegbu, I Mullaney, L Fyfe, D MacBean
Abstract:The super family of G-protein-coupled receptors (GPCRs) is the main target for the actions exerted by hormones, drugs and neurotransmitters. Each GPCR shows preferential coupling to some members of the G-protein family such as Gs, Gi and Gq which in turn activates the defined second messenger pathways. The G protein-coupled receptors (GPCRs) represent 50â€“60% of the current drug targets and this family of membrane proteins plays a crucial role in drug discovery, health and disease conditions. The G-protein-mediated signalling system has been used to study transmembrane signalling mechanisms in eukaryotic organisms resulting in different cellular activities and effects such as cellular growth, proliferation and differentiation. The G-protein-mediated signalling systems are made up of three main components, the receptors, the heterotrimeric G-proteins and the effectors in addition to various proteins that modulate the G-protein-mediated signalling process like the regulators of G-protein signalling (RGS) proteins. Mammalian cells express many GPCRs and several types of heterotrimeric G-proteins and their effectors. A number of drugs based on GPCRs have been developed for such different indications as cardiovascular, metabolic, neurodegenerative, psychiatric, and oncologic diseases. Most neurotransmitters of the central nervous system (CNS) act on GPCRs to mediate different cellular responses in normal and disease states. The activation of receptors that interact through Gi e.g. cannabinoid receptor types convey neuronal protection against hypoxic insult and resultant excitotoxic death. KEYWORDS: G-proteins, G protein coupled receptors, G protein signalling, Effectors, Neurotransmitters.
Published on: 07-04-2012