ISSN:
1432-1912
Keywords:
Tetanus
;
Iodine labeling
;
Spinal cord
;
Metabolism
;
Pharmacokinetics
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Local tetanus was elicited in rats and cats by intramuscular injection of 125I-tetanus toxin. After different times spinal radioactivity was extracted with either non-ionic (Lubrol PX) or ionic (sodium dodecyl sulfate, SDS) detergents and compared with native or 125I-toxin by gel filtration, SDS-gel electrophoresis, immunological procedures, and toxicity tests. In double-isotope experiments, 131I-toxin was added to the extracts as standard. In rats, the bulk of extracted material was indistinguishable from native toxin. However, there was a slight shift of the extracted material towards smaller molecular weights in gel filtration with Lubrol. In gel filtration with SDS, the toxin peak was followed by some tailing of 125I radioactivity. Accordingly a small part of extracted radioactivity moves faster than the standard in SDS disc gel electrophoresis. These findings taken together indicate some degradation in vivo. Adsorption to solid-phase antibodies indicated that more than 80% of the radioactivity extracted from rats was still immunoreactive. It yielded a zone confluent with extrinsic toxin in immunodiffusion. The spinal cord Lubrol extract from rats was still toxic in the expected range. Due to the very small amounts of toxin present, no precise toxicity data could be given. In cats, there was also some evidence for radioactive split products in both SDS gel filtration and disc gel electrophoresis. The patterns closely resembled those obtained with extracts from rat spinal cord. SDS extracts from rat and cat spinal cords, poisoned with 125I tetanus toxin in vivo, were also subjected to SDS disc gel electrophoresis followign reduction with dithioerythritol (DTE). They yielded large and small chains of the same size as did native toxin. In vitro, extensive degradation with brain homogenate from rats took place at pH 3.65, but not at pH 7.5. This indicates that lysosomal degradation is not a major metabolic pathway of tetanus toxin in vivo, although it is possible in principle. It is concluded that a) unlike other toxins, tetanus toxin is not necessarily degraded during its cellular uptake, b) the bulk of radioactive material is indistinguishable, following its neuronal ascent, from native or labeled toxin, c) a part of the radioactivity is recovered as split products.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00498561
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