Neuropeptide F (NPF) was first discovered in a tapeworm and two snail species and derived its name from similarities to neuropeptide Y of vertebrates. These first NPFs consist of 36-39 residues and are characterized by a C-terminal GRPRFamide pentapeptide. Later on shorter peptides with a similar C-terminus were identified in insects and named head peptides or midgut peptides, but referred to as NPF-like. A first 36mer NPF with a RVRFamide C-terminus was identified in Drosophila (Brown et al 1999). It is important here to note that the peptides referred to as short neuropeptide F (sNPF) are not ancestrally related to NPFs (see separate entry) Nässel and Wegener 2011). The first insect receptor to NPF was identified in Drosophila (NPFR1; CG1147) and is distantly related to the neuropeptide Y receptors (Garczynski et al 2002). Both NPF and the NPF receptor have been identified in many insect species, although the bona fide NPR and NPF receptor could not be found in the honeybee and Nasonia. In these species there is instead another ligand receptor system, RYamides (GKARYamide C-terminus), also discovered later in other insects. In Drosophila the RYamide (CG40733) and its receptor (NepYr, CG5811) exist in parallel with the NPF-NPFR system (see separate entry).
In Drosophila the distribution of NPF is in a small number of neurons in the brain of larvae and adults and in enteroendocrine cells of the midgut (Brown et al 1999). In other insects, such as the bug Rhodnius and the moth Heliotes zea, NPF producing neurons were additionally detected in the thoracic and abdominal ganglia, as well as in brain neurosecretory cells, suggesting a hormonal function of NPF (Gonzalez and Orchard, 2008).
Multiple functional roles have been suggested for NPF in insects. Bioassays have shown NPF to be myostimulatory in Rhodnius, and genetic evidence indicate roles in Drosophila in foraging, feeding, alcohol sensitivity, stress, aggression, reproduction, learning, as well as clock function (see Nässel and Wegener 2011). Since the NPF receptor is also expressed in Malpighian tubules of larval and adult Drosophila (FlyAtlas) this signaling system may also play a role in regulation of tubule function.
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