Orexin and Orexin Receptors

“Reverse pharmacology”, i.e., ligand identification using cell lines expressing orphan receptors, combined with genetic engineering techniques, has increased our understanding of novel signaling systems in the body. Orexin is the first and most successful example of the factors to which such an approach was applied. Our group initially identified orexin A and orexin B as endogenous peptide ligands for two orphan G-protein–coupled receptors found as human expressed sequence tags. Living in postgenome era, the success of the orexin story is driving many researchers to dig up novel bioactive peptides and their receptors for another discovery of new phases in physiology and novel opportunities for clinical treatment. This chapter discusses structures and functions of orexin neuropeptides and their receptors.