STRUCTURE-ACTIVITY-RELATIONSHIPS FOR INHIBITORY INSECT MYOSUPPRESSINS- CONTRAST WITH THE STIMULATORY SULFAKININS

Unusual among insect neuropeptides, the decapeptide myosuppressins are capable of inhibiting contractions of visceral muscle, including the isolated cockroach hindgut. The C-terminal pentapeptide Val-Phe-Leu-Ar g-Phe-NH2. has been identified as the myosuppressin active core, the m inimum number of residues required to elicit hindgut myoinhibitory act ivity. Activity of the same magnitude as the parent neuropeptide requi res the C-terminal heptapeptide fragment Asp-His-Val-Phe-Leu-Arg-Phe-N H2. Evaluation of a series of substitution analogs delineates structur al features critical for myoinhibitory activity within this important fragment. The branched, hydrophobic residues in myosuppressin position 6 (Val) and particularly position 8 (Leu), their absence in the myost imulatory sulfakinins, and the different roles played by the shared As p residue (myosuppressin position 4; leucosulfakinin position 5) in pe ptide-receptor interaction, account in large degree for the contrastin g biological activities elicited by these otherwise structurally simil ar peptide families. The results may have broad significance for other invertebrate myotropic systems, such as the locust heart and the phar yngeal retractor muscle of the mollusc Helix aspersa.