Back to Search
Start Over
The role of systemic handling in the pathophysiologic actions of botulinum toxin.
- Source :
-
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2008 Sep; Vol. 326 (3), pp. 856-63. Date of Electronic Publication: 2008 Jun 06. - Publication Year :
- 2008
-
Abstract
- The ability of botulinum toxin to poison cholinergic nerve transmission is a dynamic phenomenon that involves not only the actions of the toxin on the body but also the actions of the body on the toxin. The former has been the subject of intense research, whereas the latter has received almost no attention. Therefore, a series of studies were performed to characterize systemic handling of botulinum toxin. The results indicated that the toxin reaches the general circulation (transcytosis across epithelial cells) without obvious changes in structure or biological activity. The general circulation acts as a holding compartment until there is adequate fractional distribution to neuromuscular junctions to produce blockade of transmission. During its transit through this compartment, the toxin 1) undergoes little biotransformation, 2) does not accumulate significantly in circulating cells, and 3) remains largely in the free state. In naive animals, the t(1/2) for toxin in the general circulation is approximately 10 h, and at any given point in time, there is little uptake in nontarget organs (liver, kidney, heart, and lung). In immunized animals, toxin clearance from the general circulation is rapid, and there is substantial accumulation of antibody-antigen complexes in liver. Thus, enhanced clearance from the circulation is a major mechanism by which active immunization can protect against poisoning.
- Subjects :
- Animals
Biological Transport drug effects
Biological Transport physiology
Cells, Cultured
Epithelial Cells drug effects
Epithelial Cells metabolism
Epithelial Cells pathology
Female
Humans
Mice
Mice, Inbred BALB C
Protein Binding drug effects
Protein Binding physiology
Rabbits
Rats
Rats, Sprague-Dawley
Blood Circulation drug effects
Blood Circulation physiology
Botulinum Toxins pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1521-0103
- Volume :
- 326
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of pharmacology and experimental therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 18539649
- Full Text :
- https://doi.org/10.1124/jpet.108.136242