Bungarotoxins nicotinic acetylcholine receptor binding

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). 

Chen DN, Patrick JW (1997) The a-bungarotoxin-binding nicotinic acetylcholine receptor from rat brain contains only the a7 subunit, J Biol Chem 272 24024-24029 Clarke PBS, Schwartz RD, Paul SM, Pert CB, Pert A (1985) Nicotinic binding in rat brain autoradiographic comparison of [ H]acetylcholine, [ H]nicotine, and [ I]-alpha-bungarotoxin, J Neurosci 5 1307-1315... 

Paton WDM, Zaimis EJ (1949) The pharmacological actions of polymethylene bistrimethylammo-nium salts. Br J Pharmacol Chemother 4 381 00 Patrick J, Stallcup WB (1977) a-Bungarotoxin binding and cholinergic receptor function on a rat sympathetic nerve line. J Biol Chem 252 8629-8633 Patrick J, Boulter J, Deneris E, Wada K, Wada E, Connolly J, Swanson L, Heinemann S (1989) Structure and function of neuronal nicotinic acetylcholine receptors deduced from cDNA clones. Prog Brain Res 79 27-33... 

Balass M, Katchalski-Katzir E, Fuchs S, The a-bungarotoxin binding site on the nicotinic acetylcholine receptor analysis using a phage-epitope library, Proc. Natl. Acad. Sci. USA, 94 6054-6058, 1997. 

Use of Toxin Binding to Purify a Channel Protein a-Bungarotoxin is a powerful neurotoxin found in the venom of a poisonous snake (Bungarus multicinctus). It binds with high specificity to the nicotinic acetylcholine receptor (AChR) protein and prevents the ion channel from opening. This interaction was used to purify AChR from the electric organ of torpedo fish. 

Breese CR, Adams C, Logel J, Drebing C, Rollins Y, et al. 2000. Comparison of the regional expression of nicotinic acetylcholine receptor alpha7 mRNA and [125I]-alpha-bungarotoxin binding in human postmortem brain. J Comp Neurol 387(3) 385-398. 

Figure 7.23 Diagrammatic representation of cross section of nicotinic acetylcholine receptor showing various sites that bind acetylcholine, insecticides, toxins, and drugs. ACh, acetylcholine NTX, nereistoxin a-BGT, a-bungarotoxin H12-HTX, pH]perhydrohistrionicotoxin PCP, phencyclidine. (From Eldefrawi, M.E. and Eldefrawi, A.T., in Safe Insecticides Development and Use, Hodgson, E. and Ruhr, R.J., Eds., Marcel Dekker, New York, 1990, p. 155. With permission.)...

Court J, Spurden D, Lloyd S, McKeith I, Ballard C, Cairns N, Kerwin R, Perry R, Perry E (1999) Neuronal nicotinic receptors in dementia with Lewy bodies and schizophrenia alpha-bungarotoxin and nicotine binding in the thalamus. J Neurochem 73 1590-1597 Couturier S, Bertrand D, Matter JM, Hernandez MC, Bertrand S, MiUar N, Valera S, Barkas T, Ballivet M (1990) A neuronal nicotinic acetylcholine receptor subunit (alpha 7) is devel-opmentally regulated and forms a homo-oligomeric channel blocked by alpha-BTX. Neuron 5 847-856... 

Orth M, Amann B, Robertson MM, RothweU JC (2005) ExcitabUity of motor cortex inhibitory circuits in Tourette syndrome before and after single dose nicotine. Brain 128 1292-1300 Oswald RE, Freeman JA (1981) Alpha-bungarotoxin binding and central nervous system nicotinic acetylcholine receptors. Neuroscience 6 1-14... 

The structural similarity between onchidal (an acetate ester) and acetylcholine suggested that the toxicity of onchidal could result from inhibition of either nicotinic acetylcholine receptors or AChE. Although onchidal (1.0 mM) did not prevent the binding of 1-a-bungarotoxin to nicotine acetylcholine receptors, it inhibited AChE in a progressive, apparently irreversible, manner. The apparent affinity of onchidal for the initial reversible binding to AChE (Kd) was approximately 300 p.M, and the apparent rate constant for the subsequent irreversible inhibition of enzyme activity (Xij ct) was approximately 0.1 min ... 

The venom of the Southeast Asian banded krait (Bungarus multicinctus) contains a-bungarotoxin, which binds exclusively and by high affinity to the nicotinic receptors. By means of these and many other substances, it is unveiled that insects and other invertebrates like the vertebrates have both types of acetylcholine receptors. 

Acetylcholine receptors can be prepared from a variety of excitable tissues from animals. An example is the electric organ of electric eels, a very dense concentration of excitable tissue and a source of many neuronal receptors. A number of other chemicals competitively bind with anatoxin-a for the acetylcholine receptor (e.g., nicotine, acetylcholine itself, a-bungarotoxin) and have been radiolabeled and used in receptor binding assays for anatoxin-a. 

Batrachotoxin has no effect on a calcium channel (18), or on potassium channels (795). However, batrachotoxin does appear to antagonize the increase in conductance elicited by nicotinic agonists in striated neuromuscular preparations (111) and adrenal glands (164, 165). The mechanism involved in inhibition of nicotinic receptor-controlled conductances by batrachotoxin remains unclear but actually might represent another site of action for the alkaloid. Batrachotoxin, however, has no effect on binding of a-bungarotoxin or histrionicotoxin to the acetylcholine receptor-channel... 

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