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 suboesophageal ganglia of Helix aspersa. The inhibitory action of nine S-Iamide peptides was investigated. Structure-activity studies suggest that all act through a common receptor, which normally requires FVRIamide at the C terminal, with a preferred length of seven amino acids. Substitution at the N-terminal with alanine (A), threonine (T), proline (P) or leucine (L) results in little change in potency, suggesting the N-terminal requirements are relatively flexible. Ion substitution experiments suggest that potassium is the main ion involved in the inhibitory response to S-Iamide application. Studies using a range of compounds, which modify second messenger systems, would suggest that S-Iamide peptides may interact with adenylate cyclase. No evidence was found for an interaction with either guanylate cyclase or nitric oxide synthase.
Pedder
S M
SM
Department of Physiology and Pharmacology, School of Biological Sciences, University of Southampton, Bassett Crescent East, SO16 7PX, Southampton, UK.
Muneoka
Y
Y
Walker
R J
RJ
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000577:Amides / Q000737:chemistry / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D002712:Chlorides / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006372:Helix, Snails / Q000502:physiology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000737:chemistry* / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015290:Second Messenger Systems; D013329:Structure-Activity Relationship
D000067956:Adenylyl Cyclase Inhibitors; D000577:Amides; D002712:Chlorides; D004791:Enzyme Inhibitors; D009479:Neuropeptides; D010726:Phosphodiesterase Inhibitors; C017759:9-(tetrahydro-2-furyl)-adenine; D005576:Colforsin; D000242:Cyclic AMP; D000225:Adenine; D011188:Potassium; D015056:1-Methyl-3-isobutylxanthine