11-Oxo-tetrodotoxin and a specifically labelled 3H-tetrodotoxin.
Tetrodotoxin was oxidized to a hydrated aldehyde, 11-oxo-tetrodotoxin, which shares the specificity of tetrodotoxin for the Na+ channel of the isolated voltage-clamped frog skeletal muscle fiber, but is four to five times more potent. It binds to the solubilized Na+ channel of eel electroplax with a similarly higher potency, because of an equilibrium dissociation constant about 0.25, and a dissociation rate constant 2.4 times slower than those for tetrodotoxin. 11-Oxo-tetrodotoxin can be reduced to regenerate a tetrodotoxin, which is chemically and biologically indistinguishable from the original tetrodotoxin. By reducing with tritiated sodium borohydride, a 3H marker can be inserted regiospecifically to yield 11-[3H]-tetrodotoxin. Because it has a defined specific activity of > 2.5 Ci/mmole, and a 3H marker which does not exchange with solvent proton, 11-[3H]-tetrodotoxin is an ideal tracer for tetrodotoxin. It may enable studies of problems which require higher signals and/or better stability of the marker than those obtainable from currently available tracer Na(+)-channel ligands.
Wu
B Q
BQ
Department of Pharmacology, State University of New York, Downstate Medical Center, Brooklyn 11203-2098, USA.
Yang
L
L
Kao
C Y
CY
Levinson
S R
SR
Yotsu-Yamashita
M
M
Yasumoto
T
T
D000818:Animals; D001667:Binding, Competitive; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004305:Dose-Response Relationship, Drug; D004593:Electrophorus; D004594:Electrophysiology; D007553:Isotope Labeling; D009682:Magnetic Resonance Spectroscopy; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010084:Oxidation-Reduction; D018408:Patch-Clamp Techniques; D011522:Protons; D011896:Rana temporaria; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013779:Tetrodotoxin / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D014316:Tritium
D011522:Protons; D015222:Sodium Channels; D014316:Tritium; C104261:11-oxotetrodotoxin; D013779:Tetrodotoxin