Neuro toxins

Dennis J. McKenna and Stephen J. Peroutka. "Serotonin neuro-toxins Focus on MDMA (3,4-methylenedioxymethampheta-mine, Ecstasy )." In Serotonin Receptor Subtypes Basic and Clinical Aspects, edited by S. J. Peroutka, pp. 127 8. New York Alan R. Liss Publishers, 1990. 

Toxicological observations indicate that pulegone is an insect neuro-toxin, as well as an abortifacient in women and in animals. (15)-( — )-Pulegone is far less toxic in mice than (li )-(+) pulegone (both hepatotoxic and pneumotoxic). 

Dendrobatidae Phyllobates aurotaenia Cardiotoxin Neuro toxin Batrachotoxin Homobatrachotoxin... 

Neuro toxin Anabaena, Oscillatoria, Canada, Chine,... 

Kurtland LT (1988) Amyotrophic lateral sclerosis and Parkinson s disease complex on Guam linked to an environmental neuro toxin. Trends Neurosci 11 51—54. 

Synergy Endogenous neurotoxins display a synergistic effect, i.e. the neurotoxic concentration of ammonia always depends on the concentration of the other endogenous neuro toxins. 

Acetylcholine receptors provide another target for chemicals with neurotoxic potential most of these act as antagonists. o-Tubocurarine is the classical nicotinic receptor antagonist, and curare-like substances are found in elapid and hydrophid snakes (a-neuro-toxins) such as cobra (a-cobratoxin) and krait... 

In carboxypeptidases and thermolysins, the Zn + ligands are two histidines and one Glu C02, separated by a different number of amino-acid spacers. The Zn +-H20 activated by Glu C02 is involved in catalysis. Human leucotriene A4 hydrolase, Clostridium botulinum neuro-toxin A, and VanX D-Ala-D-Ala carboxypeptidase belong to the thermolysin family, although they do not necessarily catalyze peptidase reactions. 

Stewart, J.E., Marks, L.J., Gilgan, M.W., Pfeiffer, E., Zwicker, B.M. Microbial utilization of the neuro-toxin domoic acid blue mussels Mytilus edulis) and soft shell clams Mya arenaria) as sources of the microorganisms. Canadian Journal of Microbiology, 1998 44(5) 456-464. 

This parallels the kinetic study conclusions(52) that the two sites are initially kinetically identical with respect to toxin binding, and yet differ in reactivity toward the affinity alkylating agent, 4-(N-maleimido)-benzyltrimethylammonium iodide. The 2 1 stoichiometry and structural similarity of the toxin combining sites of AChR have been recently confirmed also by EPR studies of interaction of nonselectively spin labeled Naja naja siamensis long-type a-neuro toxin with Torpedo californica AChR solubilized protein and AChR-rich membranes(53). 

Another potential explanation for the imique epidemiology of human botulism was provided in a study of botulinum toxin binding and transcytosis across polarized monolayers of two hiunan colon carcinoma cell lines (T-84 and Caco-2). Substantial binding of iodinated BoNT/A and BoNT/B to hiunan colon carcinoma cells was observed, while minimal binding of type Cl neuro-toxin was detected (Maksymowych and Simpson, 1998). Both type A and B neurotoxins were also efficiently taken up, transcytosed, and released, by the polarized human carcinoma cells, whereas minimal transcytosis of type Cl neurotoxin was observed. The patterns of neurotoxin transcytosis (A and B, but not Cl) observed in these human gut epithelial cell lines correlate with human susceptibility to foodbome botulism (Maksymowych and... 

Ratomponirina, C., Hode, Y., Hechler, V., and Maitre, M. (1995) Gamma-hydroxybutyrate receptor binding in rat brain is inhibited by guanyl nucleotides and pertussis toxin. Neuro sci. Lett. 189, 51-53. 

The toxins produced are fast acting neuro or organ toxins absorbed via the oral route. 

Burgen ASV, Dickens F, Zatman LJ (1949) The action of botulinum toxin on the neuro-muscular junction. J Physiol 109 10-24... 

We have also determined the cytotoxicities of natural PA and the synthetic analognes 3-6 in the mouse neuroblastoma cells, Nemo-2a. Due to the limitation of availability of the componnds, the cytotoxicities were tested only at 12 pM by counting the viable cells treated with toxins for 24 h. We observed that 5 and 6 elicited more than 90% death responses, whereas PA elicited only 20% death responses, and 3 and 4 did not show cytotoxicity at this level, snggesting this cytotoxicity not to be comparable to that in mice. We proved that 5 indnced apoptosis in Neuro-2a at 12 pM within... 

Sket, D., Dettham, W-D., Clinton, M.E., Sketelj, J., Cucek, D., Brzin, M. (1991a). Prevention of diisopropylphosphoro-fluoridate-induced myopathy hy hotulinum toxin type A blockage of quantal release of acetylcholine. Acta Neuro-pathol. 82 134 2. 

As noted under the heading of general anesthetics, there are other allosteric sites that recognize re.spectively. neuro-.stcroids. barbiturates, inhalation anesthetics, alcohols and the phenol Diprivan (.separate sites). The convuLsants picro-toxin and pcntylenetetrazole have definite binding sites on GABA receptors. 

Mochida S, Poulain B, Weller U, Habermann E, Tauc L (1989) Light chain of tetanus toxin intracellularly inhibits acethylcholine release at neuro-neuronal synapses, and its internalization is mediated by heavy chain. In FEBS Lett. 253 47—51 Monk JR, Fernandez JM (1994) The exocytotic fusion pore and neurotransmitter release. In Neuron 12 707-16... 

Habermann E, Muller H, Hudel M (1988) Tetanus toxin and botulinum A and C neurotoxins inhibit noradrenaline release from cultured mouse brain. J. Neuro-chem. 51 522-7. 

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