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Biomedical subjects

L L Simpson

Publications and source records attributed to L L Simpson.

119 records · Page 7Linked to original sources
PubMed1969

Failure to inhibit in vitro or in vivo acetycholinesterase with botulinum toxin type A.

An attempt has been made to replicate an earlier finding that type A botulinum toxin can inhibit the in vitro activity of acetylcholinesterase. Two methods of enzyme assay were employed, but with neither technique were we able to reproduce the finding of in vitro enzyme inhibition. In fact, an examination of the data from the previous report leads us to question the possibility of the observations that were given. Furthermore, an investigation was carried out to determine if botulinum toxin can exert an inhibiting effect on acetylcholinesterase that is situated in the biological tissue. The answer again is negative. The experimental observations, coupled with several mathematical computations, do not support the notion that botulinum toxin is an acetylcholinesterase inhibitor.

Acetylcholinesterase↗
PubMedDate not supplied

Identification of the characteristics that underlie botulinum toxin potency: implications for designing novel drugs.

Botulinum toxin is a uniquely potent substance whose natural site of action is the peripheral cholinergic nerve ending. A substantial amount of information on the cellular, subcellular and molecular aspects of toxin action has been accumulated, and as a result a sound understanding of the basis for toxin potency has been developed. The principal characteristics of the toxin molecule that account for its potency are its ability: a) to be absorbed from the gut with minimal degradation; b) to bind to receptors that maximize the prospects of a pathophysiologic outcome; c) to act by a multiplicative (viz., enzymatic) mechanism; and d) to modify a substrate that is essential for neuronal function. Interestingly, the same properties that account for potency can also be exploited to utilize the toxin as a research tool and as a therapeutic agent. Several specific examples of ways to use the toxin advantageously are presented, including: a) development of oral medications and vaccines; b) analysis of subcellular mechanisms that govern transcytosis; c) identification of cell surface markers characteristic of cholinergic nerve endings; and d) analysis of specific aspects of exocytosis, such as spontaneous quantal release and synchronous quantal release. In all likelihood, further studies on the mechanism of botulinum toxin action will reveal yet further opportunities for utilizing it as a research tool or therapeutic agent.

Administration, Oral↗
PubMedDate not supplied

The action of botulinal toxin.

Two areas of research on botulinal toxin are reviewed: (1) isolation and characterization of the toxin molecule and (2) the mechanism by which the toxin acts to paralyze transmission by cholingerrgic nerves. The various molecules of botulinal toxin (types A, B, D, E and F) have molecular weights of approximately 150,000. The toxins are composed of two subunits with molecular weights of approximately 100,000 and approximately 50,000, respectively. The subunits are linked by one or more disulfide bonds. The large-molecular-weight substance (approximately 150,000) is fully neurotoxic; neither subunit possesses neurotoxicity. Toxin-induced paralysis of cholingergic nerves involves three steps: (1) an initial binding step that involves an external receptor; (2) a translocation step during which the toxin molecule, or some portion of it, moves through the nerve membrane; and (3) a paralytic step during which the release of acetylcholine is blocked.

Animals↗