title: Excitation evoked by FMRFamide and FLRFamide in the heart of Buccinum undatum and evidence for inositol 1,4,5-trisphosphate as an RF-tetrapeptide second messenger.
abstract: In this study the relative potencies of four established molluscan cardioexcitatory agents were examined on Buccinum heart. The potencies were, in decending order: phenylalanine-leucine-arginine-phenylalanine-NH2 (FLRFamide) > phenylalanine-methionine-arginine-phenylalanine-NH2 (FMRFamide; 80% of maximum) > 5-hydroxytryptamine (5HT; 60% of maximum) > guanosine triphosphate (GTP; 15% of maximum). FMRFamide and FLRFamide had similar dose-response curve patterns with thresholds at 10(-9) mol l(-1) but FLRFamide was more potent than FMRFamide. The superfused atrium was much less sensitive to all agonists than the internally perfused ventricle. FLRFamide and FMRFamide induced small depolarizations (1-2 mV) which triggered a burst of action potentials of about 5 mV which on reaching 4 mV triggered a burst of fast twitch contractions. Lithium, at high concentrations inhibited FMRFamide and 5-HT responses of internally perfused ventricles. Neomycin also inhibited peptide responses, but was without effect on 5-HT responses. Heparin, however, for technical reasons was without effect on ventricular responses to all three agonists. FMRFamide and FLRFamide appear to share a common receptor, the potency difference being due to the substitution of leucine for methionine in FLRFamide. The RF N-terminal sequence appears crucial for receptor activation. The Phospholipase C inhibitor neomycin equally inhibits responses to the two peptides while 5-HT responses are unaffected. This implicates a peptide/receptor interaction which activated inositol 1,4,5-trisphosphate (IP3) as a second messenger.
authors.affiliation: Department of Biological Sciences, IENS, Lancaster University, England.
authors.forename: A M
authors.initials: AM
authors.lastname: Ellis
authors.forename: H
authors.initials: H
authors.lastname: Huddart
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D018692:Antimanic Agents / Q000494:pharmacology; D049872:Bivalvia / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D019835:FMRFamide / Q000032:analysis / Q000494:pharmacology* / Q000502:physiology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018021:Lithium Chloride / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D009355:Neomycin / Q000494:pharmacology; D009842:Oligopeptides / Q000032:analysis / Q000494:pharmacology* / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
chemical_list: D000925:Anticoagulants; D018692:Antimanic Agents; D009842:Oligopeptides; D011500:Protein Synthesis Inhibitors; D012701:Serotonin; D019835:FMRFamide; C066148:phenylalanyl-leucyl-arginyl phenylalaninamide; D015544:Inositol 1,4,5-Trisphosphate; D006160:Guanosine Triphosphate; D006493:Heparin; D010738:Type C Phospholipases; D018021:Lithium Chloride; D009355:Neomycin