Acetylcholine onchidals

Onchidal and fasciculins are natural toxins, which produce their toxicity in mammalian systems by virtue of primarily acetylcholinesterase (AChE) inhibition. AChE hydrolyzes and inactivates acetylcholine, thereby regidating the concentration of the transmitter at the synapse. Termination of activation is normally dependent on dissociation of acetylcholine from the receptor and its subsequent diffusion and hydrolysis, except in diseases where acetylcholine levels are limiting or under AChE inhibition, conditions that increase the duration of receptor activation (Silver, 1963). 

One of the first interesting structures with cholinergic properties isolated from a marine source is the chemical onchidal. This compound was first isolated from the mollusc Onchidella binneyi and has an acetate ester similar to acetylcholine. Upon isolation, onchidal was discovered to be an active site-directed irreversible inhibitor of AChE (Abramson et ah, 1989). 

The structural similarity between onchidal (an acetate ester) and acetylcholine suggested that the toxicity of onchidal could result from inhibition of either nicotinic acetylcholine receptors or AChE. Although onchidal (1.0 mM) did not prevent the binding of 1-a-bungarotoxin to nicotine acetylcholine receptors, it inhibited AChE in a progressive, apparently irreversible, manner. The apparent affinity of onchidal for the initial reversible binding to AChE (Kd) was approximately 300 p.M, and the apparent rate constant for the subsequent irreversible inhibition of enzyme activity (Xij ct) was approximately 0.1 min ... 

Onchidal is an irreversible inhibitor of enzyme AChE with a novel mechanism of action. It has been suggested, however, that its toxicity could be a consequence of the inhibition of either nicotinic acetylcholine receptor or AChE enzyme. 

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