Spider toxins and methods for their use as blockers of calcium c

Drug – bio-affecting and body treating compositions – Extract – body fluid – or cellular material of undetermined... – Derived from arthropod

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424537, C07K 1500, A61K 3556

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active

051962047

ABSTRACT:
Methods and compositions for blocking various channels and receptors within an organism are provided. For example, two toxins were isolated from the Agelenopsis aperta spider. The first toxin comprised a toxin having a molecular weight of from aproximately 5,000 to approximately 10,000. This toxin was found to have an irreversible effect on calcium channels within the central nervous system. A second toxin having a molecular weight of less than about 1,000 was also isolated. This toxin was found to have a reversible blocking effect on calcium channels within the central nervous system and the cardiovascular system.
A third toxin was isolated from the Argiope aurantia spider. This toxin was found to have a reversible effect on excitatory amino acid receptors. Finally, a toxin having a molecular weight of from approximately 5,000 to approximately 7,000 daltons was isolated from the Hololena curta spider. This toxin was found to have an irreversible effect on excitatory amino acid receptors.
The present invention further relates to methods of treating heart and neurological diseases by applying the toxins isolated and identified. In particular, the low molecular weight toxin from Agelenopsis aperta may provide a treatment of certain heart conditions such as arrhythmia, angina, hypertension, and congestive heart failure. In addition, the toxins may provide beneficial effects on certain neurological conditions including seizures. It is also found that the toxins having an irreversible effect are effective as tags in probing the various components within the calcium channels and excitatory amino acid receptors and are effective insecticides and anthelmintics.

REFERENCES:
Jackson, "Effect . . . ", EAA Transmission pp. 51-54, 1987 Alan R. Liss, Inc.
Bowers, "Isolation . . . "Howard Hughs Medical Instit Lab Conference 1986.
Bowers, "Identification . . . "Proc. Natl. Acad. Sci USA, vol. 84 pp. 3506-3510, May 1987, Neurobiology.
Abe, T. et al., "Effects of a Spider Toxin on the Glutaminergic Synapse of Lobster Muscle, J. Physiol. (Lond.) 339:243-252 (1983).
Adams, Michael E. et al., "Isolation and Biological Activity of Synaptic Toxins from the Venom of the Funnel Web Spiders, Agelenopsis Aperia" (1983).
Adams, M. E. et al., "Multiple Synaptic Antagonists From the Venom of an Orb Weaver Spider," Society for Neuroscience Abstracts, paragraph 260.2, p. 946 (1986).
Bachmann, M., "Isolation and Partial Characterization of a Toxin from the Venom of the East African Orthograph Spider Pterinochilus spec., Toxicon 20:547-552 (1982).
Bateman, A. et al., "Postsynaptic Block of a Glutamatergic Synapse by Low Molecular Weight Fractions of Spider Venom," 339 Brain Research, 237 (1985).
Bowers, C. W. et al., "Isolation and Partial Characterization of a New Irreversible Presynaptic Neurotoxin from Spider Venom," Society of Neuroscience Abstracts 12:27 (1986).
Branton, W. D. et al., "New Presynaptic Neurotoxins from Spider Venom," Society of Neuroscience Abstracts 12:176 (1986).
Croucher, J. J. et al., "Anticonvulsant Action of Excitatory Amino Acid Antagonists. Science 216:899-901 (1982).
Cruz-Hofling, M. A. et al., "Effects of Phoneutria Nigriventer Spider Venom on Mouse Peripheral Nerve, Quart. J. Exp. Physiol. 70:623-640.
Duchen, L. W. et al., "The Pharmacology of Spider Venom. In: A. T. Tu(Ed.), Insect Poisons, Allergens and Other Invertebrate Venoms, Handbook of Natural Toxins, vol. 2, New York, M. Dekker, pp. 483-513 (1984).
Entwistle et al., "Isolation of a Pure Toxic Polypeptide From the Venom of the Spider Phoneutria Nigriventer and its Neurophysiological Activity on an Insect Femur Preparation, Toxicon 20:1059-1067 (1982).
Foil, L. D. et al., "Partial Characterization of Lethal and Neuroactive Components of the Brown Recluse Spider (Loxosceles Reclusa) Venom (1982).
Geren, C. R. et al., "The Biochemistry of Spider Venoms." In: A. T. Tu(Ed.), Insect Poisons, Allergens and Other Invertebrate Venoms. Handbook of Natural Toxins, vol. 2, New York, M. Dekker, pp. 441-481 (1984).
Greenamyre, J. T., "The Role of Glutamate in Neurotransmission and in Neurologic Disease," Archives of Neurology 43:1058-1063 (1986).
Jackson, H. et al., "Non-N-Methyl-D-Aspartate Receptors Mediating Synaptic Transmission in the Avian Cochlear Nucleus: Effects of Kynurenic Acid, Dipicolinic Acid and Streptomycin," 16 Neuroscience, 171 (1985).
Jackson, H. et al., "Spider Venoms Block Synaptic Transmission Mediated by Non-N-Methyl-D-Aspartate Receptors in the Avian Cochlear Nucleus," presented to the Society of Neuroscience Oct. 21, 1985.
Jackson, Hunter et al., "Presynaptic Blockade of Transmission by a Potent Long-Lasting Toxin from Aglenopsis Aperta Spiders. Society for Neuroscience Abstracts 12:730 (1986).
Kawai, Nobufumi et al., "Spider Venom Contains Specific Receptor Blocker of Glutaminergic Synapses," 247 Brain Research, 169 (1982).
Kawai, Nobufumi et al., "Effect of a Spider Toxin on Glutaminergic Synapses in the Mammalian Brain," 3 Biomedical Research, 353 (1982).
Kawai, Nobufumi et al., "Block of Glumtamate Receptors by a Spider Toxin," (1983).
Kawai, Nobufumi et al., "Blockade of Synaptic Transmission in the Squid Giant Synapse by a Spider Toxin (JSTX)," 278 Brain Research, 346 (1983).
Kawai, Nobufumi et al., "Spider Toxin (JSTX) on the Glutamate Synapse," 79 J. Physiol., Paris, 228 (1984).
Love, S. et al., "Morphological Abnormalities in Mylinated Nerve Fibers Caused by Leiurus, Centruoides and Phoneutria Venoms and Their Prevention by Tetrodotoxin. Quart. J. Exp. Physiol. 71:115-122 (1985).
Meldrum, B., "Excitatory Amino Acids and Anoxic/Ischaemic Brain Damage. Trends Neuroscience 8:47-48 (1985).
Michaelis, E. K. et al., "Spiders Venoms Inhibit L-Glutamate Binding to Brain Synaptic Membrane Receptors," 81 Proc. Natl. Acad. Sci. USA, 5571 (Sep. 1984).
Miller, R. J., "Toxin Probes for Voltage Sensitive Calcium Channels, Trends in Neuroscience 7:309 (1984).
Miller, R. J., "Multiple Calcium Channels and Neuronal Function, Science 235:46-52 (1987).
Nagai, Takatoshi et al., "Differential Blocking Effects of a Spider Toxin on Synaptic and Glutamate Responses in the Afferent Synapse of the Acoustico-lateralis Receptors of Plotosus," 300 Brain Research, 183 (1984).
Nemeth, E. F. et al., "Pharmacological Evidence for Synaptic Transmission Mediated by Non-N-Methyl-D-Aspartate Receptors in the Avian Cochlear Nucleus," 40 Neuroscience Letters, 39 (1983).
Nemeth, E. F. et al., "Evidence for the Involvement of Kainate Receptors in Synaptic Transmission in the Avian Cochlear Nucleus," 59 Neuroscience Letters, 297 (1985).
Odell, G. V. et al., "A Review of Research on Tarantula Colony Maintenance, Venom Collection, Composition and Toxicity."
Quicke, Donald L. J. et al., "Postsynaptic Blockade of Locust Neuromuscular Transmission by Low Molecular Weight Fractions of Araneid Venoms." (1985).
Rees, Riley et al., "Clinical Treatment of Confirmed Brown Recluse Spider Bits with Dapsone and Antivenom," (1985).
Rothman, S. M. et al., "Glutamate and the Pathophysiology of Hypoxic-Ischemic Brain Damage." Annals of Neurology 19:105-111 (1986).
Saito, Mitsuyoshi et al., 37 Spider Toxin (JSTX) Blocks Glutamate Synapse in Hippocamptal Pyramidal Neurons," 346 Brain Research, 397 (1985).
Schwarcz et al., "Excitatory Amino Acid Antagonists Provide a Therapeutic Approach to Neurologic Disorders. The Lancer, Jul. 20, 140-143 (1985).
Sheumack et al., "A Comparative Study of Properties and Toxic Components of Funnel Web Spider (Atrax) Venom. Comp. Biochem. Physiol. 78C:55-66 (1984).
Sperelakis, N., "Properties of Calcium-Dependent Slow Action Potentials: Their Possible Role In Arrhythmias. In: L. H. Opie (Ed.), Calcium Antagonists and Cardiovascular Disease, New York, Raven Press, pp. 277-291 (1984).
Sperelakis, N. et al., "Properties of Myocardial Calcium Slow Channels and Mechanism of Action of Calcium Antagonistic Drugs. Current Topics in Membranes and Transport," 25:44-76 (1985).
Tashumukhamedov, B. A. et al., "Effects of Different Spider Venoms on Artificial and Biological Membranes," Toxins as Tools in Neurochemistry (1983).
Tashmukhamedov, B.

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