title: Second messengers mediating mechanical responses to the FARP GYIRFamide in the fluke Fasciola hepatica.
abstract: Spontaneous phasic contractions recorded from isolated body strips of Fasciola hepatica were increased in frequency and amplitude by GYIRFamide, an FMRFamide-related peptide (FaRP). Superfusion with guanosine 5'-O-(2-thiodiphosphate) (100 microM, n = 5) reduced the effects of GYIRFamide on both frequency (by 82%) and amplitude (by 75%). The adenylate cyclase inhibitor MDL-12330A (25 microM) increased spontaneous activity. MDL-12330A completely inhibited the frequency response to GYIRFamide and reduced the amplitude response by 66% as measured relative to this elevated basal activity (n = 6). Inhibition of phospholipase C (PLC) with neomycin sulfate (1 mM) had no direct effect on activity but reduced the frequency response to GYIRFamide by 64% and the amplitude increase by 95% (n = 9). The protein kinase C (PKC) inhibitor chelerythrine chloride (10 microM) also reduced frequency and amplitude responses by 98 and 99%, respectively, without affecting basal contractility (n = 5). Phorbol 12-myristate 13-acetate, an activator of PKC, increased contraction frequency and amplitude (n = 6). It was concluded that GYIRFamide stimulates mechanical activity in F. hepatica through a G protein, via a PLC- and PKC-dependent second messenger pathway.
authors.affiliation: School of Biology and Biochemistry, Queen's University of Belfast, Belfast BT9 7BL, Northern Ireland, United Kingdom.
authors.forename: M K
authors.initials: MK
authors.lastname: Graham
authors.forename: I
authors.initials: I
authors.lastname: Fairweather
authors.forename: J G
authors.initials: JG
authors.lastname: McGeown
mesh_terms: D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005210:Fasciola hepatica / Q000502:physiology*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D007097:Imines / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D009355:Neomycin / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D010617:Phenanthridines / Q000494:pharmacology; D015290:Second Messenger Systems / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D007097:Imines; D009479:Neuropeptides; D009842:Oligopeptides; D010617:Phenanthridines; D013873:Thionucleotides; C105067:glycyl-tyrosyl-isoleucyl-arginyl-phenylalaninamide; D006153:Guanosine Diphosphate; C023427:guanosine 5'-O-(2-thiodiphosphate); C014925:RMI 12330A; C016299:chelerythrine; D009355:Neomycin