G-protein coupled receptors (GPCRs) are a diverse super-family of proteins located within the plasma membrane of eukaryotic cells which have a common architecture consisting of seven-transmembrane (7-TM) segments, connected by extracellular (ECL) and intracellular (ICL) loops. They differ from other 7-TM proteins in their ability to activate guanine-nucleotide binding proteins or β-arrestin and so initiate a signaling cascade. Therefore, they are among the most important pharmaceutical drug targets[1],[2]. GPCRs are activated by a wide variety of stimulants, including light, odorant molecules, peptide and non-peptide neurotransmitters, hormones, growth factors and lipids, and control a wide variety of physiological processes including sensory transduction, cell–cell communication, neuronal transmission, and hormonal signaling[3]. Upon activation by a stimulant (binding or conformational change of ligand), the conformation of the receptor is altered, which can result into two principal signal transduction pathways involving the G protein-coupled receptors: the cAMP signal pathway and the phosphatidylinositol signal pathway[4].
Analysis of the human genome revealed at least 799 unique GPCRs. One widely adopted scheme classify the GPCRs into six families, with the most important and extensively studied being: family A (Rhodopsin-like); family B (Secretin); family C (Metabotropic glutamate/pheromone); family D (Fungal mating hormone); family E (Cyclic AMP); family F (Frizzled/Smoothened)[5].