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.
England
L J
LJ
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143-0450, USA.
Imperial
J
J
Jacobsen
R
R
Craig
A G
AG
Gulyas
J
J
Akhtar
M
M
Rivier
J
J
Julius
D
D
Olivera
B M
BM
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