Neuronal calcium channel antagonists. Discrimination between calcium channel subtypes using omega-conotoxin from Conus magus venom

The omega-conotoxins from the venom of fish-hunting cone snails are probably the most useful of presently available ligands for neuronal Ca channels from vertebrates. Two of these peptide toxins, omega-conotoxins MVIIA and MVIIB from the venom of Conus magus, were purified. The amino acid sequences...

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Bibliographic Details
Published in:Biochemistry (Easton) 1987-04, Vol.26 (8), p.2086
Main Authors: Olivera, B M, Cruz, L J, de Santos, V, LeCheminant, G W, Griffin, D, Zeikus, R, McIntosh, J M, Galyean, R, Varga, J, Gray, W R
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Brain - metabolism
Calcium - metabolism
Calcium Channel Blockers
Cattle
Cell Membrane - metabolism
Chickens
Ion Channels - drug effects
Ion Channels - metabolism
Mollusk Venoms - chemical synthesis
Mollusk Venoms - isolation & purification
Mollusk Venoms - pharmacology
Neurons - drug effects
Neurons - metabolism
omega-Conotoxin GVIA
Synaptosomes - metabolism
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Summary:The omega-conotoxins from the venom of fish-hunting cone snails are probably the most useful of presently available ligands for neuronal Ca channels from vertebrates. Two of these peptide toxins, omega-conotoxins MVIIA and MVIIB from the venom of Conus magus, were purified. The amino acid sequences show significant differences from omega-conotoxins from Conus geographus. Total synthesis of omega-conotoxin MVIIA was achieved, and biologically active radiolabeled toxin was produced by iodination. Although omega-conotoxins from C. geographus (GVIA) and C. magus (MVIIA) appear to compete for the same sites in mammalian brain, in amphibian brain the high-affinity binding of omega-conotoxin MVIIA has narrower specificity. In this system, it is demonstrated that a combination of two omega-conotoxins can be used for biochemically defining receptor subtypes and suggested that these correspond to subtypes of neuronal Ca2+ channels.
ISSN:0006-2960
DOI:10.1021/bi00382a004