INACTIVATION OF A SEROTONIN-GATED ION-CHANNEL BY A POLYPEPTIDE TOXIN FROM MARINE SNAILS

The venom of predatory marine snails is a rich source of natural produ cts that act on specific receptors and ion channels within the mammali an nervous system. A 41-amino acid peptide, sigma-conotoxin GVIIIA, wa s purified on the basis of its ability to inactivate the 5-HT3 recepto r, an excitatory serotonin-gated ion channel. sigma-Conotoxin contains a brominated tryptophan residue, which may be important for peptide a ctivity because the endogenous Ligand for the 5-HT3 receptor is a hydr oxylated derivative of tryptophan. sigma-Conotoxin inactivates the 5-H T3 receptor through competitive antagonism and is a highly selective i nhibitor of this receptor. Serotonin receptors can now be included amo ng the molecular targets of natural polypeptide neurotoxins.