title: A nonpeptidal peptidomimetic agonist of the insect FLRFamide myosuppressin family.
abstract: Benzethonium chloride (Bztc) is the first totally nonpeptide ligand for an insect, indeed an invertebrate, peptide receptor. Bztc mimics the inhibitory physiological activity of the myosuppressins, a subfamily of the FLRFamides, in three different insect bioassay systems. The inhibitory action of leucomyosuppressin and the nonpeptide Bztc in both the cockroach hindgut and the mealworm neuromuscular junction can be blocked by the lipoxygenase inhibitor, nordihydroguaiaretic acid, providing evidence for similar modes of action. Lipoxygenase metabolites of arachidonic acid may mediate inhibition of neuromuscular transmission by these two factors. In addition, Bztc competitively displaces a radiolabeled myosuppressin analogue from high- and low-affinity receptors of the locust oviduct. Thus, the nonpeptide interacts with both binding and activating regions of myosuppressin receptors. Molecular dynamics experiments in which selected functional groups of Bztc were fit onto corresponding functional groups of low-energy myosuppressin pentapeptide structures indicate how Bztc may mimic the myosuppressins at a molecular level. The discovery of Bztc as a nonpeptidal peptidomimetic analogue provides an opportunity to develop new pest management strategies by targeting an insect's own peptide receptor.
authors.affiliation: Veterinary Entomology Research Unit, FAPRL, U.S. Department of Agriculture, Agricultural Research Service, College Station, TX 77845, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Nachman
authors.forename: E H
authors.initials: EH
authors.lastname: Olender
authors.forename: V A
authors.initials: VA
authors.lastname: Roberts
authors.forename: G M
authors.initials: GM
authors.lastname: Holman
authors.forename: D
authors.initials: D
authors.lastname: Yamamoto
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001558:Benzethonium / Q000494:pharmacology*; D003058:Cockroaches; D007213:Indomethacin / Q000494:pharmacology; D007301:Insect Hormones / Q000819:agonists / Q000494:pharmacology*; D009637:Masoprocol / Q000494:pharmacology; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009469:Neuromuscular Junction / Q000187:drug effects*; D009479:Neuropeptides / Q000819:agonists / Q000494:pharmacology*; D009842:Oligopeptides / Q000819:agonists*; D011487:Protein Conformation
chemical_list: D007301:Insect Hormones; D009479:Neuropeptides; D009842:Oligopeptides; C058650:leucomyosuppressin; D001558:Benzethonium; D016718:Arachidonic Acid; D009637:Masoprocol; C066148:phenylalanyl-leucyl-arginyl phenylalaninamide; D007213:Indomethacin