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 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.
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143-0450, USA.
L J
LJ
England
J
J
Imperial
R
R
Jacobsen
A G
AG
Craig
J
J
Gulyas
M
M
Akhtar
J
J
Rivier
D
D
Julius
B M
BM
Olivera
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001665:Binding Sites; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002460:Cell Line; D003001:Cloning, Molecular; D020916:Conotoxins; D018076:DNA, Complementary; D015640:Ion Channel Gating; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D044422:Receptors, Serotonin, 5-HT4; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012908:Snails / Q000737:chemistry*; D014364:Tryptophan / Q000032:analysis / Q000378:metabolism
D000596:Amino Acids; D001549:Benzamides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D020916:Conotoxins; D018076:DNA, Complementary; D007473:Ion Channels; D008978:Mollusk Venoms; D010456:Peptides, Cyclic; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012702:Serotonin Antagonists; C113586:alpha-conotoxin GVIIIA; C102355:contryphan; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; D014364:Tryptophan; C055971:zacopride