title: Characterization of a novel gastropod toxin (6-bromo-2-mercaptotryptamine) that inhibits shaker K channel activity.
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.
authors.affiliation: Department of Chemistry and the Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61820, USA.
authors.forename: Wayne P
authors.initials: WP
authors.lastname: Kelley
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Wolters
authors.forename: Jon T
authors.initials: JT
authors.lastname: Sack
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Jockusch
authors.forename: John C
authors.initials: JC
authors.lastname: Jurchen
authors.forename: Evan R
authors.initials: ER
authors.lastname: Williams
authors.forename: Jonathan V
authors.initials: JV
authors.lastname: Sweedler
authors.forename: William F
authors.initials: WF
authors.lastname: Gilly
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004220:Disulfides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D011994:Recombinant Proteins / Q000187:drug effects; D051637:Shaker Superfamily of Potassium Channels; D012908:Snails; D021241:Spectrometry, Mass, Electrospray Ionization; D014363:Tryptamines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014982:Xenopus laevis
chemical_list: D004220:Disulfides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011994:Recombinant Proteins; D051637:Shaker Superfamily of Potassium Channels; D014363:Tryptamines; C478480:bis(6-bromo-2-mercaptotryptamin-2-yl)disulfide