Identification in mammalian brain of an endogenous substance with Na+ channel blocking activities similar to those of tetrodotoxin.
A substance with Na+ channel blocking activities has been isolated from pig brain after extraction and purification on sulfopropyl-Sephadex C-25, reversed-phase and carboxymethyl Synchropak high pressure liquid chromatography columns. The peptidic material i) displaces [3H]ethylenediamine tetrodotoxin ([3H]en-TTX) from its binding sites on rat brain membranes, (ii) it blocks 22Na+ influx induced by veratridine and sea anemone toxin on neuroblastoma and embryonic chick heart cells in culture, (iii) it specifically decreases the height of the action potential generated in frog sciatic nerve, and (iv) it blocks the fast Na+ current in voltage-clamped neuroblastoma cells. These properties are similar to those of tetrodotoxin while the endogenous factor is a peptide that is destroyed by proteases. These results suggest the presence in pig brain of a potent Na+ channel modulation activity.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001667:Binding, Competitive; D001923:Brain Chemistry; D002645:Chickens; D002851:Chromatography, High Pressure Liquid; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D009206:Myocardium / Q000166:cytology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D010447:Peptide Hydrolases / Q000494:pharmacology; D011894:Rana pipiens; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D013552:Swine; D013779:Tetrodotoxin / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007473:Ion Channels; D009419:Nerve Tissue Proteins; D013779:Tetrodotoxin; D012964:Sodium; D010447:Peptide Hydrolases