Structure-activity and possible mode of action of S-Iamide neuropeptides on identified central neurons of Helix aspersa

Intracellular recordings were made from identified neurons from the suboeso phageal ganglia of Helix aspersa. The inhibitory action of nine S-Iamide pe ptides was investigated. Structure-activity studies suggest that all act th rough a common receptor, which normally requires FVR-Iamide at the C termin al. with a preferred length of seven amino acids. Substitution at the N-ter minal with alanine (A), threonine (T), proline (P) or leucine (L) results i n little change in potency, suggesting the N-terminal requirements are rela tively flexible. Ion substitution experiments suggest that potassium is the main ion involved in the inhibitory response to S-Iamide application. Stud ies using a range of compounds, which modify second messenger systems, woul d suggest that S-Iamide peptides may interact with adenylate cyclase. No ev idence was found for an interaction with either guanylate cyclase or nitric oxide synthase. (C) 2001 Elsevier Science B.V. All rights reserved.