Agatoxin

Agatoxins are a class of chemically diverse polyamine and peptide toxins which are isolated from the venom of various spiders. Their mechanism of action includes blockade of glutamate-gated ion channels, voltage-gated sodium channels, or voltage-dependent calcium channels. Agatoxin is named after the funnel web spider (Agelenopsis aperta) which produces a venom containing several agatoxins.

The venom of the Agelenopsis aperta is located in two glands, which are located in the two fang bases. Ejection of the venom takes place via contraction of surrounding muscles. To obtain this venom, the spider is milked by electrical stimulation. The crude venom is dissolved in an EDTA plasma to avoid proteolysis. Purification of the agatoxin is accomplished by a HPLC procedure.

Agatoxins may be divided into three major structural subclasses:

Alpha-agatoxins are composed of polyamines which are attached to an aromatic moiety (see for example AG 489).

Mu-agatoxins are C-terminally amidated peptides, consisting of 35-37 amino acids and are constrained by four intramolecular disulfide bonds.

Omega-agatoxins in turn are subdivided in four classes based on their primary structures, biochemical properties and calcium channels specificity.

In several of the omega-agatoxins contain one or more D-amino acids which are produced from L-amino acids through the action of peptide isomerases.

Alpha-agatoxin causes a rapid reversible paralysis in insects, while mu-agatoxin cause a slow long-lasting paralysis. When the two toxins will be injected at the same time, they are synergistic. So co-injection of these toxins leads to a paralysis for a very long, possible everlasting, period of time. Omega-agatoxin injection causes spasms leading to a progressive paralysis which will eventually lead to death in insects. Because insects have a much smaller repertoire of voltage-gated calcium channels and have a different pharmacology than vertebrates the effects can vary between species.

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