Bungarotoxins

Acetylcholine nicotinic (LGIC) Na+, K+ and Ca2 + conductance Nicotine, suxamethonium Tubocurarine, a-conotoxins, a-bungarotoxin... 

Peptides in the a-conotoxin family are inhibitors of nicotinic acetylcholine receptors. They were first isolated from C. geographus venom as components which cause paralysis in mice and fish when injected intraperitoneally (27). Early physiological experiments (28) indicated that a-conotoxins GI, GII, and GIA (see Table III) all act at the muscle end plate region. Mini end-plate potentials and end plate potentials evoked in response to nerve stimulation are inhibited in the presence of a-conotoxins in the nM to pM range. a-Conotoxin GI was subsequently shown to compete with rf-tubocurarine and a-bungarotoxin for the acetylcholine receptor (29). 

Radioiodinated derivatives have been prepared to define more closely the target site of a-conotoxins on the acetylcholine receptor (R. Myers, unpublished data). In membrane preparations from Torpedo electroplax, photoactivatable azidosalicylate derivatives of a-conotoxin GIA preferentially label the p and 7 subunits of the acetylcholine receptor. However, when the photoactivatable derivative is cross-linked to detergent solubilized acetylcholine receptor (AChR), only the 7 subunit is labeled. Since snake a-neurotoxins mainly bind to the a subunits of AChR and a-conotoxins compete directly with a-bungarotoxin, the cross-linking results above are both intriguing and problematic. 

Clarke, PB (1992) The fall and rise of neuronal ot-bungarotoxin binding proteins. TIPS 3(11) 407-413. 

Beta-bungarotoxin, a protein in cobra snake venom, also binds to cholinergic nerves to stop ACh release while a-bungarotoxin (from the same source) binds firmly to peripheral postsynaptic nicotinic receptors. The combined effect ensures the paralysis of the snake s victim. 

Uteshev, V. V., Stevens, D. R. Haas, H. L. (1996). Alpha-bungarotoxin-sensitive nicotinic responses in rat tuberomammillary neurons. Pflugers Arch. Bur. J. 

The nAChR subtypes vary in response to pharmacological manipulation. The a7 receptors have a low affinity for nicotine and are sensitive to a-bungarotoxin (a-BTX) antagonism, whereas the heteromeric nAChRs are not.14 The p2 containing (p2 asterisk denotes the presence of additional subunits) nAChRs have the highest affinity for nicotine binding and some selectivity for antagonism... 

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). 

S. L. Pearce and E. Hawrot, Intrinsic fluorescence of binding-site fragments of the nicotinic acetylcholine receptor Perturbations produced upon binding a-bungarotoxin, Biochemistry 29, 10649-10659 (1990). 

Figure 7,13. AChR dusters on a rat rayotube in culture, visualized with (A) rhodamine anti-43K protein (B) fluorescein-labeled a-bungarotoxin (corresponding field) (C) rhodamine-labeled anti-vinculin and (D) fluorescein-labeled g-bungarotoxin (corresponding field). The antibodies were gifts from R. Bloch. University of Maryland Medical School. Note that AChR and 43K tend to aggregate in the same regions, whereas AChR and vinculin appear to exdude each other. Additional photographs are in Ref. 107.

Fu Y, Matta SG, Sharp BM. (1999). Local alpha-bungarotoxin-sensitive nicotinic receptors modulate hippocampal norepinephrine release by systemic nicotine. J Pharmacol Exp Ther. 289(1) 133-39. Fudala PJ, Iwamoto ET. (1986). Further studies on nicotine-induced conditioned place preference in the rat. Pharmacol Biochem Behav. 25(5) 1041-49. 

Segal M, Dudai Y, Amsterdam A. (1978). Distribution of an alpha-bungarotoxin-binding cholinergic nicotinic receptor in rat brain. Brain Res. 148(1) 105-19. 

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