Biological presynaptic effect

From the earliest description of the toxin s actions on neuronal systems, it emerged that a-LTX affects specifically the presynaptic element, from which it causes massive neurotransmitter release (e.g., Longenecker et al. 1970). The toxin has no major enzymatic activities (Frontali et al. 1976). Crucially, a-LTX has been discovered to create Ca2+-permeable channels in lipid bilayers (Finkelstein et al. 1976), and a large body of evidence shows that Ca2+ influx through membrane channels induced by a-LTX in the presynaptic membrane accounts for a major part of its effect. Pore formation occurs in all the biological systems mentioned above, but the features of a-LTX-triggered release cannot be fully explained by the toxin pore. 

Abstract Presynaptic metabotropic receptors for acetylcholine and adrenaline/ noradrenaline were first described more than three decades ago. Molecular cloning has resulted in the identification of five G protein-coupled muscarinic receptors (Mi — M5) which mediate the biological effects of acetylcholine. Nine adrenoceptors (ociabd,oc2abc,Pi23) adrenafine/noradrenaline signals between cells. 

Figure 1 summarizes the different transduction mechanisms. Interestingly, adenylate cyclase, a common target of Gi/0 proteins in other biological systems, does not seem to be involved in the intracellular effects triggered by activation of presynaptic Ai adenosine receptors (Fredholm et al. 1986 Fredholm and Lindgren 1987). 

Use of lithium is based in the biological theory that bipolar disorder results from an overactivity of the neurotransmitters in the brain. Lithium appears to enhance reuptake of serotonin and norepinephrine at the presynaptic level and to decrease dopamine and norepinephrine effects at the postsynaptic receptors. 

It is not clear whether the biological effects of the toxin are all sequelae of its effects on membranes. The toxin provokes an increase in miniature end-plate potential frequency at the neuromuscular junction, leading eventually to a depletion of presynaptic vesicles [32]. Increased calcium influx as a result of toxin action on the nerve terminal may be a prime event, but it is difficult to understand the specificity of action of the toxin in the biological situation. 

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