Presynaptic toxins types

There are several types of presynaptic toxins. They are structurally distinct among themselves. However, there is one common property, and that is the possession of phospholipase A activity. Phospholipase A is one of the common enzymes found in various snake venoms and animal tissues. However, not all phospholipases A are toxic. The toxic phospholipase A is usually a basic protein. There is as yet no satisfactory explanation for this. Tsai et al. (1987) found that the basic amino acids tended to cluster near the surface region at the NH2-terminal side in basic phospholipase A. This may have something to do with toxicity. 

One type of presynaptic toxin is composed of two subunits bound together. The basic subunit has phospholipase A activity, whereas the acidic subunit has no enzymic activity. Crotoxin is the first presynaptic toxin isolated from snake venom and is also one of the most well-studied presynaptic toxins. 

The acidic and basic subunit types presynaptic toxins are fairly common in neurotoxic snake venoms. For instance, such toxins have been isolated from the venoms of C. viridis concolor (Aird et al., 1989b) and C. durissus collilineatus (Lennon and Kaiser, 1990). The... 

The third type of presynaptic toxin is a tertiary complex of three polypeptide chains. Taipoxin from the venom of the Australian snake, taipan, has three subunits, a, p, and y, with an Mr of46,000. The number of amino acid residues present in the subunits is 120, 120, and 135, respectively. The a-chain is basic and has phospholipase A activity. 

While most investigations show that sea snake neurotoxins are postsynaptic type, Gawade and Gaitonde (23) stated that Enhydrina schistosa major toxin has dual actions or postsynaptic as well as presynaptic toxicity. E, schistosa venom phospholipase A is both neurotoxic and myotoxic. Neurotoxic action of the enzyme is weak so that there is sufficient time for myonecrotic action to take place (24), Sea snake, L. semifasciata toxin also inhibits transmission in autonomic ganglia, but has no effect on transmission in choroid neurons. 

As far as the inhibitory mechanism of H3-receptors is concerned, the effect of (R)a-methylhistamine is decreased by pretreatment with pertussis toxin and, like the 012-adrenoceptor- and Aj-adenosine receptor-mediated effects, it is potentiated by oo-conotoxin GVIA, a blocker of the N-type Ca channel (Endou et al., 1994). One may conclude from these findings that presynaptic histamine H3-receptors are probably coupled to a pertussis toxin-sensitive Gi/Go protein, which exerts a negative control on the neuronal Ca++-currents, that are responsible for the exocytotic release of noradrenaline. 

Presynaptic H3 receptors also are uniform in their signal transduction. They couple to Gi/o proteins and decrease the depolarization-induced release of neurotransmitters by inhibiting multiple calcium channels (e.g., Arrang et al. 1985 Schlicker et al. 1994 Endou et al. 1994 Brown and Haas 1999 see Stark et al. 2004). For comparison, the signal transduction of soma-dendritic H3 autoreceptors in histamin-ergic neurons also involves a pertussis toxin-sensitive G-protein with subsequent inhibition of N- and P-type Ca2+ channels (Takeshita et al. 1998). The few exceptions to this signal transduction pathway are discussed in the corresponding subsections below (see Sections 3.1, 3.3, and 3.9). 

The seven types of botulinum toxin " and the tetanus toxin " are the most neurotoxic substances known. Only 10 molecules are sufficient to kill a mouse. Both toxins are zinc proteases, which block presynaptic transmitter release by cleaving specific synaptic vesicles proteins (see p. 1780 and Fig. 

Two types of illness are associated with the botulinum toxin, infant and adult botulism. An adult becomes iU by eating spoiled food that contains the toxin. Infants become ill from eating the spores of the botulinum bacterium. One source of these spores comes from the ingestion of honey. Spores are not normally toxic to adults. Botulinum toxins work by binding to the presynaptic nerve terminal at the neuromuscular junction and at cholinergic autononuc sites. They then act to stop the release of acetylchloline presynaptically, thus blocking neurotransmission. 

We initially sought to explain the biochemical basis of venom-induced insect paralysis by spider venom components. Using an electrophysiological assay for synaptic transmission, we deflned three classes of ion channel specific toxins, the a-, p- and co-agatoxins from Agelenopsis aperta venom. Two different types of co-agatoxins (Types I and II) were found to block insect presynaptic calcium channels. 

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