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

• Published in: Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology Biochemical, systemic, and environmental physiology, 2000-09, Vol.170 (5-6), p.351-356
• Main Authors: Ellis, A M, Huddart, H
• Format: Article
• Language: English
• Subjects: Animals; Anticoagulants - pharmacology; Antimanic Agents - pharmacology; Bivalvia - physiology; Buccinum undatum; Dose-Response Relationship, Drug; FMRFamide - analysis; FMRFamide - pharmacology; FMRFamide - physiology; Guanosine Triphosphate - pharmacology; Heparin - pharmacology; Inositol 1,4,5-Trisphosphate - antagonists & inhibitors; Inositol 1,4,5-Trisphosphate - metabolism; Lithium Chloride - pharmacology; Marine; Membrane Potentials - drug effects; Membrane Potentials - physiology; Myocardial Contraction - drug effects; Myocardial Contraction - physiology; Myocardium - chemistry; Myocardium - metabolism; Neomycin - pharmacology; Oligopeptides - analysis; Oligopeptides - pharmacology; Oligopeptides - physiology; Protein Synthesis Inhibitors - pharmacology; Second Messenger Systems - drug effects; Second Messenger Systems - physiology; Serotonin - pharmacology; Type C Phospholipases - antagonists & inhibitors
• ISSN: 0174-1578; 1432-136X
• DOI: 10.1007/s003600000110

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.