Toxins postsynaptic

The primary structure of postsynaptic toxins is unique to snakes, and there are no homologies with the toxins of scorpions, spiders, or bees. However, there is an interesting report that significant homologous sequences to snake postsynaptic neurotoxins are found in visna virus and HIV-I tat proteins (Gourdou et al., 1990). 

The similarity of the primary structure of different sea snake venoms has already been discussed. Postsynaptic neurotoxins from Elapidae venom have been extensively studied. Elapidae include well-known snakes such as cobra, krait, mambas, coral snakes, and all Australian snakes. Like sea snake toxins, Elapidae toxins can also be grouped into short-chain (Type I) and long-chain (Type II) toxins. Moreover, two types of neurotoxins are also similar to cardiotoxins, especially in the positions of disulfide bonds. However, amino acid sequences between cardiotoxins and sea snake and Elapidae neurotoxins are quite different. In comparing the sequence of sea snake and Elapidae neurotoxins, there is a considerable conservation in amino acid sequence, but the difference is greater than among the various sea snake toxins. 

When a nerve-muscle preparation is stimulated in the presence of a sea snake neurotoxin, there is no twitch. However, when the muscle itself is stimulated directly in the presence of a neurotoxin, the muscle contracts. This means that neurotoxin does not inhibit the muscle itself. Moreover, postsynaptic neurotoxin does not inhibit the release of acetylcholine from the nerve ending. Therefore, the site of snake toxin inhibition must be in the postsynaptic site 20). Later it was shown that a neurotoxin strongly binds to the acetylcholine receptor (AChR). 

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. 

Mixture of neurotoxins that block the acetylcholine receptors. The /3-bungarotoxin is a pre-synaptic neural toxin, a-bungarotoxin is a postsynaptic neural toxin, and K-bungarotoxin is specific to the neuronal receptors in ganglions. They are obtained from the venom of the banded krait (Bungarus multicinctus). 

This chapter deals with botulinum toxin type A (BOTOX) in the treatment of strabismus, blepharospasm, and related disorders. Botulinum toxin type A (BOTOX) has been used to treat strabismus, blepharospasm, Meige s syndrome, and spasmodic torticollis. By preventing acetylcholine release at me neuromuscular junction, botulinum toxin A usually causes a temporary paralysis of the locally injected muscles. The variability in duration of paralysis may be related to me rate of developing antibodies to me toxin, upregulation of nicotinic cholinergic postsynaptic receptors, and aberrant regeneration of motor nerve fibers at me neuromuscular junction. Complications related to this toxin include double vision (diplopia) and lid droop (ptosis). 

An action potential in the presynaptic fiber propagates into the synaptic terminal and activates voltage-sensitive calcium channels in the membrane of the terminal (Figure 6-3). The calcium channels responsible for the release of transmitter are generally resistant to the calcium channelblocking agents discussed in Chapter 12 Vasodilators the Treatment of Angina Pectoris (verapamil, etc) but are sensitive to blockade by certain marine toxins and metal ions (Tables 12-4 and 21-1). Calcium flows into the terminal, and the increase in intraterminal calcium concentration promotes the fusion of synaptic vesicles with the presynaptic membrane. The transmitter contained in the vesicles is released into the synaptic cleft and diffuses to the receptors on the postsynaptic... 

Blier P, Lista A de Montigny C. Differential properties of pre- and postsynaptic 5-hydroxytryptamine receptors in the dorsal raphe and hippocampus II.elfect of pertussis and cholera toxins. J Pharmacol Exp Ther 1993 265 16-23. 

One of the most important hydrolases is acetylcholine esterase (cholinesterase). Acetylcholine is a potent neurotransmitter for voluntary muscle. Nerve impulses travel along neurons to the synaptic cleft, where acetylcholine stored in vesicles is released, carrying the impulse across the synapse to the postsynaptic neuron and propagating the nerve impulse. After the nerve impulse moves on, the action of the neurotransmitter molecules must be stopped by cholinesterase, which hydrolyzes acetylcholine to choline and acetic acid. Some dangerous toxins such as the exotoxin of Clostridium botulinum and saxitoxin interfere with cholinesterase, and many nerve agents such as tabun and sarin act by blocking the hydrolytic action of cholinesterase, see also Enzymes Hydrolysis. 

---