title: Analogs of sulfakinin-related peptides demonstrate reduction in food intake in the red flour beetle, Tribolium castaneum, while putative antagonists increase consumption.
abstract: The insect sulfakinins (SKs) constitute a family of neuropeptides that display both structural and functional similarities to the mammalian hormones gastrin and cholecystokinin (CCK). As a multifunctional neuropeptide, SKs are involved in muscle contractions as well as food intake regulation in many insects. In the red flour beetle Tribolium castaneum, the action on food intake by a series of synthetic SK analogs and one putative antagonist was investigated by injection in beetle adults. The most remarkable result was that both sulfated and non-sulfated SKs [FDDY(SO3H)GHMRFamide] inhibited food intake by about 70%. Strong activity observed for SK analogs featuring a residue that mimics the acidic nature of Tyr(SO3H) but lack the phenyl ring of Tyr, indicate that aromaticity is not a critical characteristic for this position of the peptide. SK demonstrated considerable tolerance to Ser and Ala substitution in position 8 (basic Arg), as analogs featuring these uncharged substitutions retained almost all of the food intake inhibitory activity. Also, the Phe in position 1 could be replaced by Ser without complete loss of activity. Conversely, substitution of Met by Nle in position 7 led to inactive compounds. Finally, the Caenorhabditis elegans sulfated neuropeptide-like protein-12 (NLP-12), that shares some sequence similarities with the SKs but features a Gln-Phe-amide rather than an Arg-Phe-amide at the C-terminus, elicited increased food intake in T. castaneum, which may indicate an antagonist activity. Co-injection of NLP-12 with nsSK blocked the food intake inhibitory effects of nsSK.
authors.affiliation: Department of Crop Protection, Faculty of Bioscience Engineering, Ghent University, 9000 Ghent, Belgium.
authors.forename: Na
authors.initials: N
authors.lastname: Yu
authors.forename: Veronica
authors.initials: V
authors.lastname: Benzi
authors.forename: Moises João
authors.initials: MJ
authors.lastname: Zotti
authors.forename: Dorien
authors.initials: D
authors.lastname: Staljanssens
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kaczmarek
authors.forename: Janusz
authors.initials: J
authors.lastname: Zabrocki
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Nachman
authors.forename: Guy
authors.initials: G
authors.lastname: Smagghe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000494:pharmacology*; D004435:Eating; D002149:Energy Intake / Q000187:drug effects*; D019476:Insect Proteins / Q000737:chemistry / Q000494:pharmacology*; D009479:Neuropeptides / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014231:Tribolium / Q000187:drug effects* / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D019476:Insect Proteins; D009479:Neuropeptides