Characterization of the Ptychodiscus brevis Polyether Neurotoxin Binding Component in Excitable Membranes.

Abstract

The polyether lipid-soluble toxins isolated from the marine dinoflagellate Ptychodiscus brevis (formerly Gymnodinium breve) bind to a unique site, Site V, associated with voltage-dependent sodium channels in rat brain synaptosomes. Using tritiated PbTx-3 as a specific probe for binding at Site V, a Kd of 2.9 nM and a Bmax of 6.8 pmoles/mg synaptosomal protein has been determined. Binding equilibria and displacement by unlabeled PbTx-3 occur in a comparable concentration range to that of saxitoxin (site I). Labeled toxin can be displaced in a competitive manner by any of the other 5 naturally-occuring toxins; the quantitative displacement ability of each appears to reflect individual potency in fish bioassay. Preliminary Ki calculations have been made for four of the toxins. Two separate photoaffinity probes have been synthesized and have been synthesized and have been covalently-linked to PbTx-3. Each complete photoaffinity-toxin conjugate competitively displaces tritiated PbTx-3 from its specific binding site, with approximate ED50's in the 20-50 nM concentration ranges.

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Document Details

Document Type
Technical Report
Publication Date
Jul 31, 1987
Accession Number
ADA184989

Entities

People

  • Daniel G. Baden
  • Thomas J. Mende

Organizations

  • University of Miami

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Acetic Acid
  • Albumins
  • Alcohols
  • Alkanes
  • Anhydrides
  • Assays
  • Bioassay
  • Biomedical Research
  • Chemical Synthesis
  • Chemistry
  • Chromatography
  • Displacement
  • Fish
  • Liquid Chromatography
  • Materials
  • Organic Chemistry
  • Pharmacology

Fields of Study

  • Biology
  • Chemistry

Readers

  • Microbial Pathology
  • Molecular and Cellular Biochemistry