Neurotoxicity receptors

Dioxins are prominent members of the class of polychlorinated hydrocarbons that also includes diben-zofuran, biphenyls and others. Dioxins are highly toxic environmental contaminants. Like others small planar xenobiotics, some dioxins bind with high affinity to the arylhydrocarbon (Ah) receptor. Dioxins activate the receptor over a long time period, but are themselves poor substrates for the enzymes which are induced via the Ah-receptor. These properties of the dioxins and related xenobiotics may be important for the toxicity of these compounds. Dioxins like 2,3,7,8-tetrachloro-p-dibenzodioxin can cause persistent dermatosis, like chloracne and may have other neurotoxic, immunotoxic and carcinogenic effects. 

Becker C-M (1992) Convulsants acting at the inhibitory glycine receptor. In Herken H, Hucho F (eds) Selective neurotoxicity. Handbook of experimental pharmacology, vol 102. Springer, Heidelberg, pp 539-575... 

Agrawal AK, Anand M, Zaidi NE, et al. 1983. Involvement of serotonergic receptors in endosulfan neurotoxicity. Biochem Pharmacol 32 3591-3593. 

Turning now to chemical attack, many predators immobilize their prey by injecting toxins, often neurotoxins, into them. Examples include venomous snakes, spiders, and scorpions. Some spider toxins (Quick and Usherwood 1990 Figure 1.3) are neurotoxic through antagonistic action upon glutamate receptors. The venom of some scorpions contains polypeptide neurotoxins that bind to the sodium channel. 

Over 40 different types of polypeptide toxins have been found in marine animals (i). Many of these toxins are exquisitely selective in their actions, affecting a single process or receptor at minute concentrations. So far the sea anemone and gastropod Conus) toxins have attracted the most attention as molecular probes of ion channels. In this chapter, we discuss several approaches which are being used to investigate, at the molecular level, the interactions of the sea anemone neurotoxic polypeptides with sodium channels. 

In order to understand the exact mechanism of the neurotoxic action, it is important to know the secondary structure of the neurotoxins as well. It is now known that postsynaptic neurotoxins attach to the a-subunits of acetylcholine receptor (AChR). 

Although Tat may directly interact with receptors on neurons, the major pathway for Tat-mediated neurotoxicity in vitro is thought to occur through a direct interaction... 

Bachis A, Mocchetti I (2004) The chemokine receptor CXCR4 and not the N-methyl-D-aspartate receptor mediates gpl20 neurotoxicity in cerebellar granule cells. J Neurosci Res 75(1) 75-82... 

Lynch DR, Guttmann RP (2002) Excitotoxicity perspectives based on N-methyl-D-aspartate receptor subtypes. J Pharmacol Exp Ther 300(3) 717-723 Magnuson DS, Knudsen BE, Geiger JD, Brownstone RM, Nath A (1995) Human immunodeficiency virus type 1 tat activates non-N-methyl-D-aspartate excitatory amino acid receptors and causes neurotoxicity. Ann Neurol 37(3) 373-380 Mamdouh Z, Chen X, Kerini LM, Maxfield FR, Muller WA (2003) Targeted recycling of PECAM from endothelial surface-connected compartments during diapedesis. Nature 421(6924) 748-753... 

D Apuzzo M, Relink A, Loetscher M, Hoxie JA, Clark-Lewis I, Melchers F, Baggiolini M, Moser B (1997) The chemokine SDF-1, stromal cell-derived factor 1, attracts early stage B cell precursors via the chemokine receptor CXCR4. Eur J Immunol 27 1788-1793 Dawson VL, Dawson TM, Uhl GR, Snyder SH (1993) Human immunodeficiency virus type 1 coat protein neurotoxicity mediated by nitric oxide in primary cortical cultures. Proc Natl Acad Sci USA 90 3256-3259... 

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