The mosquito Anopheles gambiae is in important vector for malaria, which is one of the most serious human parasitic diseases in the world, causing up to 2.7 million deaths yearly. To contribute to our understanding of A. gambiae and to the transmission of malaria, we have now cloned four evolutionarily related G protein-coupled receptors (GPCRs) from this mosquito and expressed them in Chinese hamster ovary cells. After screening of a library of thirty-three insect or other invertebrate neuropeptides and eight biogenic amines, we could identify (de-orphanize) three of these GPCRs as: an adipokinetic hormone (AKH) receptor (EC50 for A. gambiae AKH, 3 x 10(-9) M), a corazonin receptor (EC50 for A. gambiae corazonin, 4 x 10(-9) M), and a crustacean cardioactive peptide (CCAP) receptor (EC50 for A. gambiae CCAP, 1 x 10(-9) M). The fourth GPCR remained an orphan, although its close evolutionary relationship to the A. gambiae and other insect AKH receptors suggested that it is a receptor for an AKH-like peptide. This is the first published report on evolutionarily related AKH, corazonin, and CCAP receptors in mosquitoes. (c) 2006 Elsevier Inc. All rights reserved.