FUNCTIONAL GENOMICS, THE SEARCH FOR NOVEL NEUROTRANSMITTERS AND NEUROPEPTIDES

Functional genomics can be defined as the search for the physiological role of a gene for which only its primary sequence is known. Most of the genes encoding proteins containing seven hydrophobic stretches cod e for G protein-coupled receptors (GPCRs), Although many of these have been shown to interact with known natural ligands, several bind ligan ds,which have not been thus far isolated. These are the so-called orph an GPCRs, As an example of functional genomics, an 'orphan receptor st rategy' has been del eloped to identify the natural ligands of orphan GPCRs. The application of this strategy is bound to revolutionize our understanding of the diversity of the primary messengers which modulat e synaptic transmission, This review discusses the basic concepts and some of the particular problems associated with the orphan receptor st rategy. The strategy's potential is exemplified by its successes which culminated in the discovery of the neuropeptides 'orphanin FQ/nocicep tin' and 'orexins/hypocretins'. The steps that led to the characteriza tion of these neuropeptides are discussed as are some of the further s tudies that have addressed the roles of these neuropeptides. To conclu de, some of the implications of the application of the orphan receptor strategy are discussed. (C) 1998 Federation of European Biochemical S ocieties.