Characterization of a novel gastropod toxin (6-bromo-2-mercaptotryptamine) that inhibits shaker K channel activity

J Biol Chem. 2003 Sep 12;278(37):34934-42. doi: 10.1074/jbc.M301271200. Epub 2003 Jun 18.

Abstract

A novel potassium channel antagonist has been purified from the defensive mucus secreted by Calliostoma canaliculatum, a marine snail found in the temperate coastal waters of the western Pacific. The toxin is expelled from the hypobranchial gland as part of a defensive response and is contained within a viscous matrix that minimizes dilution and degradation. The active compound was isolated by multistage microbore HPLC separations followed by bioactivity assays. Nuclear magnetic resonance, combined with electrospray ionization Fourier-transform ion cyclotron resonance and electrospray ionization ion trap mass spectrometry indicate that the active component is a heretofore unknown indole-derivative, a disulfide-linked dimer of 6-bromo-2-mercaptotryptamine (BrMT). Exudates from the hypobranchial glands of various marine mollusks have been sources for dye compounds such as 6-6 dibromoindigo, the ancient dye Tyrian purple. BrMT represents the first correlation of a hypobranchial gland exudate with a molecular response. Voltage clamp experiments with a number of K channel subtypes indicate that BrMT inhibits certain voltage-gated K channels of the Kv1 subfamily.

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

  • Animals
  • Chromatography, High Pressure Liquid
  • Disulfides / chemistry
  • Disulfides / isolation & purification
  • Disulfides / pharmacology*
  • Female
  • Magnetic Resonance Spectroscopy
  • Oocytes / drug effects
  • Oocytes / physiology
  • Potassium Channel Blockers / chemistry
  • Potassium Channel Blockers / isolation & purification
  • Potassium Channel Blockers / pharmacology*
  • Potassium Channels / physiology*
  • Recombinant Proteins / drug effects
  • Shaker Superfamily of Potassium Channels
  • Snails
  • Spectrometry, Mass, Electrospray Ionization
  • Tryptamines / chemistry
  • Tryptamines / isolation & purification
  • Tryptamines / pharmacology*
  • Xenopus laevis

Substances

  • Disulfides
  • Potassium Channel Blockers
  • Potassium Channels
  • Recombinant Proteins
  • Shaker Superfamily of Potassium Channels
  • Tryptamines
  • bis(6-bromo-2-mercaptotryptamin-2-yl)disulfide