Multiple receptor sites for a molluscan peptide (FMRFamide) and related peptides of Helix

1. The membrane actions of some tetrapeptide amides and heptapeptide amides chemically related to the molluscan neuropeptides Phe-Met-Arg-Phe-NH2 (FMRFamide) and p-Glu-Asp-Pro-Phe-Leu-Arg-Phe-NH2 (pQDPFLRFamide) were tested and compared on identified neurones of Helix aspersa. 2. The C-terminal sequence -Phe-NH2 was an important requirement for each of the four different actions studied: slow increase in K conductance (gK), fast increase in gK, increase in Na conductance (gNa) and decrease in gK. 3. The response of some neurones involved a combination of such actions. 4. The tetrapeptide amides FMRFamide, Phe-Leu-Arg-Phe-NH2 (FLRFamide) and Phe-Ile-Arg-Phe-NH2 (FIRFamide) were more potent than the heptapeptide amides at producing the slow increase in gK and also produced the increase in gNa, not seen at all with the heptapeptide amides. 5. The heptapeptide amides induced the fast increase in gK which was not observed with the tetrapeptide amides. 6. Evidence is presented that each of the tetrapeptide amides tested acts on the same receptor type which mediates the increase in gNa and on which the heptapeptides were inactive. 7. The results are interpreted in terms of multiple receptors each of which however appears to require the C-terminal sequence Phe-Met(or Leu)-Arg-Phe-NH2, as has been shown for some molluscan muscle preparations which react to these peptide amides (Price & Greenberg, 1980).