title: Mode of action of a Drosophila FMRFamide in inducing muscle contraction.
abstract: Drosophila melanogaster is a model system for examining the mechanisms of action of neuropeptides. DPKQDFMRFamide was previously shown to induce contractions in Drosophila body wall muscle fibres in a Ca(2+)-dependent manner. The present study examined the possible involvement of a G-protein-coupled receptor and second messengers in mediating this myotropic effect after removal of the central nervous system. DPKQDFMRFamide-induced contractions were reduced by 70% and 90%, respectively, in larvae with reduced expression of the Drosophila Fmrf receptor (FR) either ubiquitously or specifically in muscle tissue, compared with the response in control larvae in which expression was not manipulated. No such effect occurred in larvae with reduced expression of this gene only in neurons. The myogenic effects of DPKQDFMRFamide do not appear to be mediated through either of the two Drosophila myosuppressin receptors (DmsR-1 and DmsR-2). DPKQDFMRFamide-induced contractions were not reduced in Ala1 transgenic flies lacking activity of calcium/calmodulin-dependent protein kinase (CamKII), and were not affected by the CaMKII inhibitor KN-93. Peptide-induced contractions in the mutants of the phospholipase C-β (PLCβ) gene (norpA larvae) and in IP3 receptor mutants were similar to contractions elicited in control larvae. The peptide failed to increase cAMP and cGMP levels in Drosophila body wall muscles. Peptide-induced contractions were not potentiated by 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, and were not antagonized by inhibitors of cAMP-dependent or cGMP-dependent protein kinases. Additionally, exogenous application of arachidonic acid failed to induce myogenic contractions. Thus, DPKQDFMRFamide induces contractions via a G-protein coupled FMRFamide receptor in muscle cells but does not appear to act via cAMP, cGMP, IP3, PLC, CaMKII or arachidonic acid.
authors: Department of Biological Sciences, Brock University, 500 Glenridge Avenue, St Catharines, ON, Canada, L2S 3A1.
authors: Maja
authors: M
authors: Milakovic
authors: Department of Biological Sciences, Brock University, 500 Glenridge Avenue, St Catharines, ON, Canada, L2S 3A1.
authors: Kiel G
authors: KG
authors: Ormerod
authors: Department of Anatomy & Neurobiology, Washington University, St Louis, MO 63110, USA.
authors: Markus K
authors: MK
authors: Klose
authors: Department of Biological Sciences, Brock University, 500 Glenridge Avenue, St Catharines, ON, Canada, L2S 3A1 amercier@brocku.ca.
authors: A Joffre
authors: AJ
authors: Mercier
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000502:physiology*; D019835:FMRFamide / Q000378:metabolism*; D009119:Muscle Contraction; D011498:Protein Precursors / Q000378:metabolism*; D018010:Receptors, Invertebrate Peptide / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C055209:FMRFamide receptor; D011498:Protein Precursors; D018010:Receptors, Invertebrate Peptide; C121685:aspartyl-prolyl-lysyl-glutaminyl-aspartyl-phenylalanyl-methyonyl-arginyl-phenylalanylamide; D016718:Arachidonic Acid; D019835:FMRFamide; D000242:Cyclic AMP; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D010738:Type C Phospholipases; D006152:Cyclic GMP
keywords: CaMKII; FMRFamide; G-protein coupled receptor; cAMP; cGMP; neuropeptide