Pharmacology of the molluscan cardioexcitatory neuropeptide FMRFamide

Abstract

1. 1. FMRFamide (phenylalanyl-methionyl-arginyl-phenylalanine amide) has positive inotropic and chronotropic actions on the isolated heart of the clam Mercenaria mercenaria. In addition, it causes a sustained contraction of the radula protractor muscle of the whelk Busycon contrarium. 2. 2. The action of 5-hydroxytryptamine (5-HT) is similar to that of FMRFamide on the Mercenaria heart, and the two dose-response curves are parallel. But 5-HT cardioexcitation is blocked by methysergide: that of FMRFamide is not. 3. 3. Acetylcholine (ACh) also contracts the radula protractor; but the effect is qualitatively different from that of FMRFamide and the dose-response curves are not parallel. Benzoquinonium blocks ACh contractures, but not those of FMRFamide. 4. 4. A number of amino acid derivatives and peptides were screened for biological activity on these two muscles; most were inactive (⩽ 10 −5M). In particular, analogs without the C-terminal phenylalanyl residue, or even without the amide were inactive. However, analogs with an N-acylated amino terminal residue, or with an acyl group substituted for the N-terminal residue, or even lacking one or two N-terminal residues were effective. Several peptides with biological actions in mammals were tested, but all were inactive (⩽ 10 −5M).