Fasciculin, acetylcholinesterase inhibition

Bourne, Y., Taylor, P. and Marchot, P. Acetylcholinesterase inhibition by fasciculin. Crystal structure of the complex. Cell 83 503-512,1995. 

Dajas, F., Bolioli, B., Castello, M.E., Silveira, R. (1987). Rat striatal acetylcholinesterase inhibition by fasciculin (a polypeptide fi-om green mamba snake venom). Neurosci. Lett. 77 87-91. 

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). 

Duran, R., Cervenansky, C., Dajas, F., Tipton, K.F. (1994). Fasciculin inhibition of acetylcholinesterase is prevented by chemical modification of the enzyme at a peripheral site. Biochim. Biophys. Acta 1201 381-8. 

The toxin binds to acetylcholinesterase and renders acetylcholine unhydrolyzed. This causes continuous excitement of the muscle. The inhibition of acetylcholinesterase is seen not only in vitro, but also in vivo. For instance, 80% of the acetylcholinesterase activity in the locus coeruleus was inhibited by the injection of fasciculin 2 in rats (Abo et al., 1989). The inhibition of the enzyme by fasciculin is longlasting, and a 74% inhibition five days after injection was observed (Quillfeldt et al., 1990). 

By inhibiting acetylcholinesterase, fasciculin increased the amplitude and time course of the endplate potential (Lee et al., 1985). Fasciculin also increased the amplitude of the miniature endplate potential (Cervenansky et al., 1991). 

Because of the inhibition of acetylcholinesterase, dendrotoxins or other facilitatory toxins enhance the release of acetylcholine. Thus, dendrotoxins and fasciculins have synergistic action that enhances the lethality. 

Abo, V, Viera, L., Silveira, R., and Dajas, F. (1989). Effects of local inhibition of locus caeruleus acetylcholinesterase by fasciculin in rats. Neurosci. Lett. 98 253-257. 

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