Ion of 26RFa or QRFP stimulates food intake in mouse, rat and chicken (Chartrel et al., 2003; Takayasu et al., 2006; Ukena et al., 2010). GPR103 mRNA can also be detected within a quantity of hypothalamic and extrahypothalamic regions (Takayasu et al., 2006; Bruzzone et al., 2007). Adhesion G Protein-Coupled Receptor D1 (GPR133) Proteins Storage & Stability Consistent with the widespread distribution in the receptor, 26RFa and QRFP have already been located to regulate many physiological functions such as energy homeostasis (Chartrel et al., 2016), bone formation (Baribault et al., 2006), hypothalamo-pituitary-gonadal activity (Navarro et al., 2006; Patel et al., 2008), insulin secretion (Egido et al., 2007; Granata et al., 2014; Pr ost et al., 2015), locomotor activity (Do Rego et al., 2006) and analgesia (Yamamoto et al., 2008). The prospective implication of these neuropeptides in different pathologies has prompted medicinal chemists to study the structure ctivity relationships (SAR) of 26RFa so as to design selective agonists and antagonists (Le Marec et al., 2011; Neveu et al., 2012, 2014; Georgsson et al., 2014, 2015; Nordqvist et al., 2014).26RFa/QRFP peptidesDiscoverySince the identification of FMRFamide in bivalve mollusc ganglia by Price and Greenberg (1977), a big number of FMRFamide-like peptides (FLPs) ending with all the RFamide sequence happen to be characterized in a variety of classes of invertebrates which includes cnidarians (Grimmelikhuijzen et al., 2004), plathelminths (McVeigh et al., 2005; Mousley et al., 2005), nematodes (McVeigh et al., 2006; Husson et al., 2007; Peymen et al., 2014), annelids (Salzet, 2001), molluscs (L ez-Vera et al., 2008; Bigot et al., 2014) and arthropods (Roller et al., 2008; Verleyen et al., 2009; Christie, 2015; Christie and Chi, 2015). Typically, every invertebrate FLP gene encodes a precursor protein that has the potential to generate a number of mature FLPs of variable length, from four to 45 amino acids (Walker et al., 2009; Alpha-1 Antitrypsin 1-5 Proteins Species Orchard and Lange, 2013). Moreover, each and every invertebrate species normally possesses numerous FLP genes. For example, in Caenorhabditis elegans, no less than 33 genes encoding 70 distinct FLPs have already been characterized (Li, 2005; Husson et al., 2007; Masler, 2013). In addition to genuine FLPs which include the RFamide signature at their C-terminal end, quite a few invertebrate neuropeptides terminate in rg yr H2 (RYa), rg rp H2 (RWa) or xx he H2 (XFa), X getting a Gly, Ser, Cys, Ala, Met, Val, Leu, Ile, Thr or Tyr residue (Walker et al., 2009). These peptides exert a vast array of biological activities on various26RFa/QRFP-QRFP receptorBJPorgans and tissues, notably the nervous system, heart, muscular plexus, digestive tract and reproductive method (Mercier et al., 2003; McVeigh et al., 2006; Orchard and Lange, 2013; Peymen et al., 2014). The amount of FLPs characterized in vertebrates is significantly lower than in invertebrates (Orchard and Lange, 2013). In mammals, 5 distinct genes, designated farp-1 to farp-5 (Dockray, 2004), encoding seven FLPs have been identified so far (Quillet et al., 2016). The first two mammalian FLPs, NPFF and NPAF, have been isolated from bovine brain (Yang et al., 1985) utilizing a nonselective antibody directed against FMRFamide (Dockray et al., 1983). Molecular cloning on the cDNA encoding NPFF revealed that NPFF and NPAF originate from the identical gene termed farp-1 (Perry et al., 1997; Vilim et al., 1999). NPFF and NPAF modulate the anti-nociceptive action of morphine by way of activation of two GPCRs named NPFF receptor type1 (NPFF1) and NPFF receptor type-2 (NPFF2) (Bon.