EFFECTS OF SEROTONIN ON THE TOXIN OF CLOCSTRIDIUM BOTULINUM

¹ Laboratory of Immunology, Albert Einstein Medical Center, Philadelphia, Pennsylvania

Serotonin creatinine sulfate injected into mice and followed 30 to 60 min later by an injection of botulinum toxin significantly increases the survival the of these animals. Serotonin antagonists abolish this toxin-inhibiting effect of serotonin. An experiment tending to test whether serotonin acts on the toxin directly suggested that there is no interaction between the reagent and the toxin. Furthermore, that the observed phenomenon is not due to vasoconstricting properties of serotonin was established by time fact that no more toxin was retained in the circulation of serotonin-treated mice than was found in controls, nor did mice pretreated with vasopressin survive longer than controls without vasopressin. Serotonin (5-hydroxy-tryptamine) is a neurohumoral agent which, according to Woolley and Gommi (1965), is a transmitter of Ca⁺⁺ through cell membranes. Ca⁺⁺ in turn triggers the release of acetylcholine at the end-organs of the myoneural junction. Botulinum toxin inhibits the release of acetyicholine at the same end-organs. We have demonstrated that some tryptophan residues in the toxin are either located in or contributing to the formation of reactive sites of the toxin. If serotonin also transmits Ca⁺⁺ through the nerve cell membrane, a working hypothesis may be advanced, suggesting that, owing to the close resemblance of the chemical structure of serotonin and the reactive site of botulinum toxin, the two substances compete for the attachment sites on the nerve cell.