The role of systemic handling in the pathophysiologic actions of botulinum toxin.
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.
Al-Saleem
Fetweh H
FH
Department of Medicine, Jefferson Medical College, 1020 Locust Street, Room 314, Philadelphia, PA 19107, USA.
Ancharski
Denise M
DM
Ravichandran
Easwaran
E
Joshi
Suresh G
SG
Singh
Ajay K
AK
Gong
Yujing
Y
Simpson
Lance L
LL
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001775:Blood Circulation / Q000187:drug effects* / Q000502:physiology*; D001905:Botulinum Toxins / Q000493:pharmacokinetics*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
D001905:Botulinum Toxins