The impacts of G protein-coupled receptors (GPCRs) from social, therapeutic, and economic points of view are enormous. The broad range of GPCRs covers all areas of modern medicine. The effects of point mutations, overexpression or perturbed regulation of GPCR function, and their overstimulation or inhibition affect such areas as cardiovascular, metabolic, neurodegenerative, psychiatric, and viral diseases and cancers. Currently, more than 50% of drug targets are based on GPCRs and annual worldwide sales reached $47 billion in 2003. The increase is anticipated to continue.

Novel mechanisms of GPCR action through dimerization and the continuous deorphanization of orphan GPCRs may lead to discovery of novel drug interactions and help fuel continued interest by the pharmaceutical industry. Furthermore, the success of structural biology in providing the means to achieve tailor-made structure-based drug design will soon come of age for GPCRs. The first structure of a natively isolated GPCR was solved in 2000 and, based on strong indications, a breakthrough in high-resolution structures for recombinantly expressed GPCRs is at our door step. This will further intensify the drug development programs focused on GPCRs because it will lead to discovery of better medicines with improved efficacy and better selectivity along with fewer side effects.

The physiological roles of GPCRs and their involvements, sometimes with other proteins, in various human diseases are described in this book. The chapters also present current approaches in drug discovery that include target selection, establishment of screening and functional assays, recombinant GPCR expression for drug screening and structural biology, different methods to obtain structures of GPCRs, and the importance of bioinformatics. Despite serious editing, some overlap of certain topics could not be avoided. In fact, some duplication was intentionally permitted so that each chapter could function as an independent unit.

We would like to thank all the chapter authors for their valuable contributions to this book. It has been a pleasure to work with them and inspiring to observe the positive attitudes and enthusiasm for this project. Finally, we are grateful to CRC Press and especially to Anita Lekhwani, senior acquisitions editor, chemistry, Jill Jurgensen, production coordinator, and Robert Sims, project editor, for publishing this book.

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