Inactivation of a serotonin-gated ion channel by a polypeptide toxin from marine snails

Science. 1998 Jul 24;281(5376):575-8. doi: 10.1126/science.281.5376.575.

Abstract

The venom of predatory marine snails is a rich source of natural products that act on specific receptors and ion channels within the mammalian nervous system. A 41-amino acid peptide, final sigma-conotoxin GVIIIA, was purified on the basis of its ability to inactivate the 5-HT3 receptor, an excitatory serotonin-gated ion channel. final sigma-Conotoxin contains a brominated tryptophan residue, which may be important for peptide activity because the endogenous ligand for the 5-HT3 receptor is a hydroxylated derivative of tryptophan. final sigma-Conotoxin inactivates the 5-HT3 receptor through competitive antagonism and is a highly selective inhibitor of this receptor. Serotonin receptors can now be included among the molecular targets of natural polypeptide neurotoxins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / analysis
  • Animals
  • Benzamides / pharmacology
  • Binding Sites
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Cell Line
  • Cloning, Molecular
  • Conotoxins*
  • DNA, Complementary
  • Ion Channel Gating
  • Ion Channels / antagonists & inhibitors*
  • Molecular Sequence Data
  • Mollusk Venoms / chemistry
  • Mollusk Venoms / genetics
  • Mollusk Venoms / isolation & purification
  • Mollusk Venoms / pharmacology*
  • Peptides, Cyclic / pharmacology
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT3
  • Receptors, Serotonin, 5-HT4
  • Recombinant Fusion Proteins / antagonists & inhibitors
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Proteins / antagonists & inhibitors
  • Serotonin / metabolism
  • Serotonin / pharmacology
  • Serotonin Antagonists / chemistry
  • Serotonin Antagonists / isolation & purification
  • Serotonin Antagonists / pharmacology*
  • Snails / chemistry*
  • Tryptophan / analysis
  • Tryptophan / metabolism

Substances

  • Amino Acids
  • Benzamides
  • Bridged Bicyclo Compounds, Heterocyclic
  • Conotoxins
  • DNA, Complementary
  • Ion Channels
  • Mollusk Venoms
  • Peptides, Cyclic
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Serotonin Antagonists
  • alpha-conotoxin GVIIIA
  • contryphan
  • Receptors, Serotonin, 5-HT4
  • Serotonin
  • Tryptophan
  • zacopride