© 2002 Nature Publishing Group

The G-protein-coupled receptors (GPCRs) are the largest class of cell-surface receptors and are encoded by>1,000 genes in the human genome1. GPCRs are activated by a diverse array of ligands, including hormones, peptides, amino acids, ions and photons of light, and transduce signals through a wide range of effectors. Not surpris-ingly, these receptors carry out a multitude of tasks in the central nervous system (CNS) and the periphery. Numerous diseases and disorders have been linked to mutations and POLYMORPHISMS in GPCRs2,3, and they are the targets of an increasingly large number of therapeutic agents. It has been estimated that 50 % of all modern drugs1 and almost one-quarter of the top 200 best-selling drugs in 2000 modulate GPCR activity4. GPCRs can be grouped on the basis of sequence homology into severa