Abstract
The snake neurotoxins α-bungarotoxin (α-BGT) and β-bungarotoxin (β-BGT) which act at the neuromuscular junction, were found to bind to IgE antibodies directed against neuromuscular blocking (NMB) drugs in the sera of two patients who had experienced lifethreatening anaphylactic reactions to succinylcholine. α-BGT inhibited IgE-binding to a choline-Sepharose solid support in one patient better than the NMB drug alcuronium, choline, triethylcholine and β-BGT. IC50s for α-BGT and succinylcholine were 16 and 10 nmol respectively for one patient and 34 and 6.0 nmol for the other.
Recognition of the NMB drugs and α-BGT by the same antibody is the first demonstration of an antigenic similarity between these drugs and the protein toxin.
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E.A. Barnard, J. Wieckowski andT.N. Chiu,Cholinergic receptor molecules and cholinesterase molecules at mouse skeletal muscle junctions, Nature234, 207–209 (1971).
D.K. Berg, R.B. Kelly, P.B. Sargent, P. Williamson andZ.W. Hall,Binding of α-bungarotoxin to acetylcholine receptors in mammalian muscle, Proc. Nat. Acad. Sci.69, 147–151 (1972).
D.M. Fambrough andH.C. Hartzell,Acetylcholine receptors: number and distribution at neuromuscular junctions in rat diaphragm, Science176, 189–191 (1972).
J. Patrick, S.F. Heinemann, J. Lindstrom, D.R. Schubert andJ.H. Steinbach,Appearance of acetylcholine receptors during differentiation of a myogenic cell line, Proc. Nat. Acad. Sci.69, 2762–2766 (1972).
A.J. Sytkowski, Z. Vogel andM.W. Nirenberg,Development of acetylcholine receptor clusters on cultured muscle cells, Proc. Nat. Acad. Sci.70, 270–274 (1973).
J.O. Dolly andE.A. Barnard,Purification and characterization of an acetylcholine receptor from mammalian skeletal muscle, Biochemistry16, 5053–5060 (1977).
J.P. Changeux, M. Kasai andC.Y. Lee,Use of a snake venom toxin to characterize the cholinergic receptor protein, Proc. Nat. Acad. Sci.67, 1241–1247 (1970).
R. Miledi, P. Molinoff andL.T. Potter,Isolation of the cholinergic receptor protein of Torpedo electric tissue, Nature229, 554–557 (1971).
D. Mebs, K. Narita, S. Iwanaga, Y. Samejima andC.Y. Lee,Purification, properties and amino acid sequence of α-bungarotoxin from the venom of Bungarus multicinctus, Hoppe-Seyler's Z. Physiol. Chem.353, 243–262 (1972).
C.Y. Lee,Chemistry and pharmacology of polypeptide toxins in snake venoms, Ann. Rev. Pharmacol.12, 265–286 (1972).
P. Taylor,Neuromuscular blocking agents. In:The Pharmacological Basis of Therapeutics, 6th edition (Ed.A. Goodman Gilman,L.S. Goodman andA. Gilman) pp 220–234. MacMillan, New York 1980.
T. Heidmann andJ.P. Changeux,Structural and functional properties of the acetylcholine receptor protein in its purified and membrane-bound states, Ann. Rev. Biochem.47, 317–357 (1978).
B.A. Baldo andM.M. Fisher,Substituted ammonium ions as allergenic determinants in drug allergy, Nature306, 262–264 (1983).
B.A. Baldo andM.M. Fisher,Detection of serum IgE antibodies that react with alcuronium and tubocurarine after lifethreatening reactions to muscle relaxant drugs, Anaesth. Intens. Care11, 194–197 (1983).
D.G. Harle, B.A. Baldo andM.M. Fisher,Detection of IgE antibodies to suxamethonium after anaphylactoid reactions during anaesthesia, Lancet i, 930–932 (1984).
D.G. Harle, B.A. Baldo andM.M. Fisher,Assays for, and cross-reactivities of, IgE antibodies to the muscle relaxants gallamine, decamethonium and succinylcholine (suxamethonium). J. Immunol. Methods78, 293–305 (1985).
B.A. Baldo andM.M. Fisher,Anaphylaxis to muscle relaxant drugs: cross-reactivity and molecular basis of binding of IgE antibodies detected by radioimmunoassay, Molec. Immunol.20, 1393–1400 (1983).
D.G. Harle, B.A. Baldo andM.M. Fisher,Cross-reactivity of metocurine, atracurium, vecuronium and fazadinium with IgE antibodies from patients unexposed to these drugs but allergic to other myoneural blocking drugs, Br. J. Anaesth.57, 1073–1076 (1985).
B.A. Baldo, D.G. Harle andM.M. Fisher,In vitro diagnosis and studies on the mechanism(s) of anaphylactoid reactions to muscle relaxant drugs, Ann. Fr. Anesth. Réanim.4, 139–145 (1985).
R.R. Neubig, N.D. Boyd andJ.B. Cohen,Conformations of Torpedo acetylcholine receptor associated with ion transport and desensitization, Biochemistry21, 3460–3467 (1982).
R.E. Sheridan andH.A. Lester,Fuctional stoichiometry at the nicotinic receptor, J. Gen. Physiol.80, 499–516 (1982).
D. Bovet,Synthetic inhibitors of neuromuscular transmission, chemical structures and structure activity relationships. In:Neuromuscular Blocking and Stimulating Agents Vol. 1, International Encyclopedia of Pharmacology and Therapeutics, Section 14, (Ed.J. Cheymol), pp 143–294. Pergamon Press, Oxford 1972.
R.B. Kelly andF.R. Brown III,Biochemical and physiological properties of a purified snake venom neurotoxin which acts presynaptically, J. Neurobiology5, 135–150 (1974).
P. Lesca andC. Paoletti,A protein inhibitor of acid deoxyribonucleases, Proc. Nat. Acad. Sci.64, 913–919 (1969).
M. Laskowski andM. Laskowski Jr,Naturally occurring trypsin inhibitors, Advan. Protein Chem.9, 203–242 (1954).
D. Tsernoglou andG. Petsko,The crystal structure of a post-synaptic neurotoxin from sea snake at 2.2 Å resolution, FEBS lett.68, 1–4 (1976).
B.W. Low, H.S. Preston, A. Sato, L.S. Rosen, J.E. Searl, A.D. Rudko andJ.S. Richardson,Three dimensional structure of erabutoxin b neurotoxic protein: inhibitor of acetylcholine receptor, Proc. Nat. Acad. Sci.73, 2991–2994 (1976).
D. Tsernoglou andG. Petsko,Three dimensional structure of neurotoxin a from venom of the Philippines sea snake, Proc. Nat. Acad. Sci.74, 971–974 (1977).
G.K. Wang, S. Molinaro andJ. Schmidt,Ligand responses of α-bungarotoxin binding sites from skeletal muscle and optic lobe of the chick, J. Biol. Chem.253, 8507–8512 (1978).
G.A. Grant andV.A. Chiappinelli,ϰ-Bungarotoxin: complete amino acid sequence of a neuronal nicotinic receptor probe, Biochem.24, 1532–1537 (1985).
L. Saiani, H. Kageyama, B.M. Conti-Tronconi andA. Guidotti,Purification and characterization of a bungaro-toxin polypeptide which blocks nicotinic receptor function in primary culture of adrenal chromaffin cells, Molec. Pharmacol.25, 327–334 (1984).
E.A. Kabat,Structural concepts in Immunology and Immunochemistry, 2nd edition. Holt, Rinehart and Winston, New York 1976.
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Harle, D.G., Baldo, B.A. & Fisher, M.M. Antigenic similarity between the protein neurotoxin α-bungarotoxin and neuromuscular blocking drugs. Agents and Actions 18, 512–517 (1986). https://doi.org/10.1007/BF01964956
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DOI: https://doi.org/10.1007/BF01964956