Molecular cloning and functional expression of the first insect FMRFamide receptor

FMRFamide and FMRFamide-related neuropeptides are extremely widespread and abundant in invertebrates and have numerous important functions. Here, we have cloned a Drosophila orphan receptor, and stably expressed it in Chinese hamster ovary cells. Screening of a peptide library revealed that the receptor reacted with high affinity to FMRFamide (EC(50), 6 × 10(−9) M). The intrinsic Drosophila FMRFamide peptides are known to be synthesized as a large preprohormone, containing at least 13 related FMRFamide peptides (8 distinct FMRFamides). Screening of these intrinsic Drosophila FMRFamides showed that the receptor had highest affinity to Drosophila FMRFamide-6 (PDNFMRFamide) (EC(50), 9 × 10(−10) M), whereas it had a somewhat lower affinity to Drosophila FMRFamide-2 (DPKQDFMRFamide) (EC(50), 3 × 10(−9) M) and considerably less affinity to the other Drosophila FMRFamide-related peptides. To our knowledge, this article is the first report on the molecular identification of an invertebrate FMRFamide receptor.