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

In this study the relative potencies of four established molluscan cardioex citatory agents were examined on Buccinum heart. The potencies were, in dec ending order: phenylalanine-leucine-arginine-phenylalanine-NH2 (FLRFamide) > phenylalanine-methionine-arginine-phenylalanine-NH2 (FMRFamide; 80% of ma ximum) > 5-hydroxytryptamine (5HT; 60% of maximum) > guanosine triphosphate (GTP; 15% of maximum). FMRFamide and FLRFamide had similar dose-response c urve patterns with thresholds at 10(-9) mol l(-1) but FLRFamide was more po tent than FMRFamide. The superfused atrium was much less sensitive to all a gonists than the internally perfused ventricle. FLRFamide and FMRFamide ind uced small depolarizations (1-2 mV) which triggered a burst of action poten tials 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 pepti de responses, but was without effect on 5-HT responses. Heparin, however, f or technical reasons was without effect on ventricular responses to all thr ee 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 acti vation. The Phospholipase C inhibitor neomycin equally inhibits responses t o the two peptides while 5-HT responses are unaffected. This implicates a p eptide/receptor interaction which activated inositol 1,4,5-trisphosphate (I P3) as a second messenger.