ABSTRACT

INTRODUCTION Since the pioneering work of Langley (1) and Enrlich (2) at the beginning of 20th century, identification and understanding of receptors, especially G-proteincoupled receptors (GPCRs) and their ligands, have grown to be one of the most important research areas of the academic environment and pharmaceutical industry. GPCRs are the largest family of integral membrane proteins that mediate most of the cell-cell communication in humans. GPCRs have evolved to recognize a broad variety of extracellular stimuli such as neurotransmitters, hormones, peptides, amino acids, lipids, and ions, and act to transmit messages encoded in stimuli from the exterior to the interior of the cells. GPCRs are also called seven transmembrane (7TM) receptors because they share a common feature of seven transmembrane domains (Fig. 1), and couple to cellular heterotrimeric guanine-nucleotide-binding protein (G-proteins) to elicit cellular responses. Because GPCRs are expressed on the cell membrane, signaling through GPCRs in the central nervous and peripheral systems underscores the physiological importance of this receptor family. It has been shown that numerous diseases and disorders have been linked to mutation and dysfunction of Gproteins and GPCRs (3,4), and some inherited endocrine diseases can be treatable with specific ligands targeting specific GPCRs (3).