Abstract
1. We review the pharmacological actions of toxins present in the venom of the aggressive spider Phoneutria nigriventer.
2. This venom is rich in toxins that affect ion channels and neurotransmitter release. Voltage-gated sodium, calcium, and potassium channels have been described as the main targets of these toxins.
3. In addition to these classical actions Phoneutria toxins have also been shown to affect glutamate transporter.
4. It is expected that molecular genetics in addition to biochemical, biophysical and pharmacological approaches will help to further define Phoneutria toxins and their mechanisms of action in the near future.
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REFERENCES
Araujo, D. M., Cordeiro, M. N., Diniz, C. R., and Beirao, P. S. L. (1993). Effects of a toxic fraction, PhTx2, from the spider Phoneutria nigriventer on the sodium current. Naunyn. Schmiedebergs Arch. Pharmacol. 347:205–208.
Brazil, V., and Vellard, J. (1925). Contribui¸cão ao estudo das aranhas. Mem. Inst. Butantan 1:1–70.
Cardoso, F. C., Pacifico, L. G., Carvalho, D. C., Vistória, J. M. N., Chávez-Olortegui, C., Gomez, M. V., and Kalapothakis, E. (submitted). Molecular cloning and characterization of Phoneutria nigriventer toxins active on calcium channels.
Carneiro, A.M. D., Kushmerick, C., Koenen, J., Arndt, M. H. L., Cordeiro, M. N., Olorregui, C. C., Diniz, C. R., Gomez, M. V., Kalapothakis, E., Prado, M. A. M., and Prado, V. F. (in press). Expression of a functional recombinat Phoneutria nigriventer toxin active on potassium channels. Toxicon.
Cassola, A. C., Jaffe, H., Fales, H. M., Castro, A. S., Magnoli, F., and Cipolla-Neto, J. (1998). Omegaphonetoxin-IIA: A calcium channel blocker from the spider Phoneutria nigriventer. Pflugers Arch. 436:545–552.
Catterall, W. A. (2000). Structure and regulation of voltage-gated Ca2+ channels. Annu. Rev. Cell Dev. Biol. 16:521–555.
Cordeiro, M. N., de Figueiredo, S. G., Valentim, A. C., Diniz, C. R., von Eickstedt, V. R., Gilroy, J., and Richardson, M. (1993). Purification and amino acid sequences of six Tx3 type neurotoxins from the venom of the Brazilian “armed” spider Phoneutria nigriventer (Keys). Toxicon 31:35–42.
Cordeiro, M. N., Diniz, C. R., Valentim, A. C., Von Eickstedt, V. R. D., Gilroy, J., and Richardson, M. (1992). The purification and amino acid sequences of four Tx2 neurotoxins from the venom of the Brazilian “armed” spider Phoneutria nigriventer (Keys.). FEBS 310:153–156.
Costa, S. K., Moreno, R. A., Esquisatto, L. C., Juliano, L., Brain, S. D., De Nucci, G., and Antunes, E. (2002). Role of kinins and sensory neurons in the rat pleural leukocyte migration induced by Phoneutria nigriventer spider venom Neurosci Lett 318:158–162.
Cruz-Hofling, M. A., Love, S., Brook, G., and Duchen, L. W. (1985). Effects of Phoneutria nigriventer spider venom on mouse peripheral nerve. Q. J. Exp. Physiol. 70:623–640.
de Figueiredo, S. G., de Lima, M. E., Nascimento-Cordeiro M., Diniz, C. R., Patten, D., Halliwell, R. F., Gilroy, J., and Richardson, M. (2001). Purification and amino acid sequence of a highly insecticidal toxin from the venom of the brazilian spider Phoneutria nigriventer which inhibits NMDA-evoked currents in rat hippocampal neurones. Toxicon 39:309–317.
de Figueiredo, S. G., Lima-Perez Garcia, M. E., Valentim, A. C., Cordeiro, M. N., Diniz, C. R., and Richardson, M. (1995). Purification and amino acid sequence of the insecticidal neurotoxin TX4(6-1) from the venom of the “armed” spider Phoneutria nigriventer (Keys). Toxicon 33:83–93.
dos Santos, R. G., van Rebterghen, C., Martin-Moutot, N., Masuelle, P., Cordeiro, M. N., Diniz, C. R., Mori, Y., de Lima, M. E., and Seagar, M. (2002). Phoneutria nigriventer omega Phonetoxin IIA blocks the Cav2 family of calcium channels and interacts ith omega-conotoxin biding sites. J. Biol. Chem. 277:13856–13862.
Diniz, C. R., Cordeiro, M.N., Junior, L. R., Kelly,P., Fischer, S., Reimann,F., Oliveira, E.B., and Richardson M. (1990). The purification and amino acid sequence of the lethal neurotoxin Tx1 from the venom of the Brazilian “armed” spider Phoneutria nigriventer. FEBS Lett. 263:251–253.
Diniz, M. R. V., Paine, M. J. I., Diniz, C. R., Theakston, R. D. G., and Crampton, J. M. (1993). Sequence of the DNA coding for the lethal neurotoxin Tx1 from the Brazilian “armed” spider Phoneutria nigriventer predicts the synthesis and processing of a preprotoxin. J. Biol. Chem. 268:15340–15342.
Ertel, E. A., Campbell, K. P., Harpold, M. M., Hofmann, F., Mori, Y., Perez-Reyes, E., Schwartz, A., Snutch, T. P., Tanabe, T., Birnbaumer, L., Tsien, R.W., and Catterall, W. A. (2000). Nomenclature of voltage-gated calcium channels. Neuron 25:533–535.
Ertel, E. A., Warren, V. A., Adams, M. E., Griffin, P. R., Cohen, C. J., and Smith, M. M. (1994). Type III omega-agatoxins: A family of probes for similar binding sites on L-and N-type calcium channels. J. Biochem. 33:5098–5108.
Fontana, M. D., Vital-Brazil, O., and Vital-Brazil, O. (1985). Mode of action of Phoneutria nigriventer spider venom at the isolated phrenic nerve-diaphragm of the rat. Braz. J. Med. Biol. Res. 18:557–565.
Gomez, R. S., Casali, T. A., Romano-Silva, M. A., Cordeiro, M. N., Diniz, C. R., Moraes-Santos, T., Prado, M. A., and Gomez, M. V. (1995). The effect of PhTx3 on the release of 3H-acetylcholine induced by tityustoxin and potassium in brain cortical slices and myenteric plexus. Neurosci. Lett. 196:131–133.
Guatimosim, C., Romano-Silva, M. A., Cruz, J. S., Beirao, P. S., Kalapothakis, E., Moraes-Santos, T., Cordeiro, M. N., Diniz, C. R., Gomez, M. V., and Prado, M. A. (1997). A toxin from the spider Phoneutria nigriventer that blocks calcium channels coupled to exocytosis. Br. J. Pharmacol. 122:591–597.
Kalapothakis, E., Penaforte, C. L., Beirão, P. S. L., Romano-Silva, M. A., Cruz, J. S., Prado, M. A. M., Guimarães, P. E.M., Gomez, M. V., and Prado, V. F. (1998a). Cloning of cDNAs encoding neurotoxic peptides from the spider Phoneutria nigriventer. Toxicon 36:1843–1850.
Kalapothakis, E., Penaforte, C. L., Leão, R. M., Cruz, J. S., Prado, V. F., Cordeiro, M. N., Diniz, C. R., Romano-Silva, M. A., Prado, M. A. M., Gomez, M. V., Beirão, P. S. L. (1998b). Cloning, cDNA sequence analysis and patch clamp studies of a toxin from the venom of the spider Phoneutria nigriventer. Toxicon 36:1971–1980.
Kidokoro, Y. (1975). Spontaneous calcium action potentials in a clonal pituitary cell line and their relationship to prolactin secretion. Nature 258:741–742.
Kushmerick, C., Kalapothakis, E., Beirao, P. S., Penaforte, C. L., Prado, V. F., Cruz, J. S., Diniz, C. R., Cordeiro, M. N., Gomez, M. V., Romano-Silva, M. A., and Prado, M. A. (1999). Phoneutria nigriventer toxin Tx 3-1 blocks A-type K+ currents controlling Ca2+ oscillation frequency in GH3 cells. J. Neurochem. 72:1472–1481.
Kushmerick, C., Mesquita de Carvalho, F., de Maria, M., Massensini, A. R., Romano-Silva, M. A., Gomez, M. V., Kalapothakis, E., Prado, M. A. (2001). Effects of a Lasiodora spider venom on Ca2+ and Na+ channels. Toxicon 39:991–1002.
Leao, R. M., Cruz, J. S., Diniz, C. R., Cordeiro, M. N., and Beirao, P. S. (2000). Inhibition of neuronal high-voltage activated calcium channels by the omega-Phoneutria nigriventer Tx3-3 peptide toxin. Neuropharmacology 39:1756–1767.
Love, S., and Cruz-Hofling, M. A. (1986). Acute swelling of nodes of Ranvier caused by venoms which slow inactivation of sodium channels. Acta Neuropathol. (Berl.) 70:1–9.
Love, S., Cruz-Hofling, M. A., and Duchen, L.W. (1986). Morphological abnormalities in myelinated nerve fibres caused by Leiurus, Centruroides and Phoneutria venoms and their prevention by tetrodotoxin. Q. J. Exp. Physiol. 71:115–122.
Lucas, S. (1988). Spiders in Brazil. Toxicon 26:759–772.
Ly, J., and Yn, J. (1976). L-glutamate as an excitatory transmitter at the Drosophila larval neuromuscular junction. J. Physiol. 262:215–236.
Mafra, R. A., Figueiredo, S. G., Diniz, C. R., Cordeiro, M. N., Cruz, J. D., and De Lima, M. E. (1999). PhTx4, a new class of toxins from Phoneutria nigriventer spider venom, inhibits the glutamate uptake in rat brain synaptosomes. Brain Res. 831:297–300.
Martin-Eauclaire, M. F., Cearo, B., Ribeiro, A. M., Diniz, C. R., Rochat, H., and Bougis, P. E. (1992). Molecular cloning and nucleotide sequence analysis of a cDNA encoding the main beta-neurotoxin from the venom of the south American scorpion Tityus serrulatus. Febs letter. 18:;302(3):220–222.
Matavel, A, Cruz, J. S., Penaforte, C. L., Araujo, D. A., Kalapothakis, E., Prado, V. F., Diniz, C. R., Cordeiro, M. N., Beirao, P. S. (2002). Electrophysiological characterization and molecular identification of the Phoneutria nigriventer peptide toxin PnTx2-6. FEBS Lett. 523:219–223.
Miller, R. J. (2001). Rocking and rolling with Ca2+ channels. Trends Neurosci. 24:445–449.
Mintz, I. M., Venema, V. J., Swiderek, K. M., Lee, T. D., Bean, B. P., and Adams, M. E. (1992). P-type calcium channels blocked by the spider toxin omega-Aga-IVA. Nature 355:827–829.
Miranda, D. M., Romano-Silva, M. A., Kalapothakis, E., Diniz, C. R., Cordeiro, M. N., Santos, T. M., Prado, M. A. M., and Gomez, M. V. (1998). Phoneutria nigriventer toxins block tityustoxin-induced calcium influx in synaptosomes. Neuroreport 9:1371–1373.
Moura. J. R., Prado, M. A. M., Gomez, M. V., Kalapothakis, E., Diniz, C. R., Cordeiro, M. N., and Romano-Silva, M. A. (1998). Investigation of the effect of PhTx2, from the venom of the spider Phoneutria nigriventer, on the release of [3H]-acetylcoline from rat cerebrocortical synaptosomes. Toxicon 36:1189–1192.
Newcomb, R., Szoke, B., Palma, A., Wang, G., Chen, X., Hopkins, W., Cong, R., Miller, J., Urge, L., Tarczy-Hornoch, K., Loo, J. A., Dooley, D. J., Nadasdi, L., Tsien, R.W., Lemos, J., and Miljanich, G. (1998). Selective peptide antagonist of the class E calcium channel from the venom of the tarantula Hysterocrates gigas. Biochemistry 37:15353–15362.
Olivera, B. M., Miljanich, G. P., Ramachandran, J., and Adams, M. E. (1994). Calcium channel diversity and neurotransmitter release: The omega-conotoxins and omega-agatoxins. Annu. Rev. Biochem. 63:823–867.
Penaforte, C. L., Prado, V. F., Prado, M. A. M., Romano-Silva, M. A., Guimarães, P. E., De Marco, L. A., Gomez, M. V., and Kalapothakis, E. (2000). Molecular cloning of cDNAs encoding insecticidal neurotoxic peptides from the spider Phoneutria nigriventer. Toxicon 38:1443–1449.
Perlman, D., and Halvorson, H. O. (1983) A putative signal petidase site and sequence in eukaryotic and procaryotic signal peptides. J. Mol. Biol. 167:391–409.
Prado, M. A.M., Guatimosim, C., Gomez, M. V., Diniz, C. R., Cordeiro, M. N., and Romano-Silva, M. A. (1996).Anovel tool for the investigation of glutamate release from rat cerebrocortical synptosomes: The toxin Tx3-3 from the venom of the spider Phoneutria nigriventer. Biochem. J. 314:145–150.
Price-Carter, M., Gray, W. R., and Goldenberg, D. P. (1996). Folding of omega-conotoxins. 2. Influence of precursor sequence and protein disulfide isomerase. Biochemistry 35(48):15547–57.
Reis, H. J., Gomez, M. V., Kalapothakis, E., Diniz, C. R., Cordeiro, M. N., Prado, M. A.M., and Romano-Silva, M. A. (2000). Inhibition of glutamate uptake by Tx3-4 is dependent on the redox state of cysteine residues. Neuroreport 11:2191–2194.
Reis,H. J., Prado, M.A., Kalapothakis, E., Cordeiro, M.N., Diniz, C. R., DeMarco, L. A., Gomez, M.V., and Romano-Silva, M. A. (1999). Inhibition of glutamate uptake by a polypeptide toxin (phoneutriatoxin 3-4) from the spider Phoneutria nigriventer. Biochem. J. 343:413–418.
Rezende, L., Jr., Cordeiro M. N., Oliveira E. B., and Diniz, C. R. (1991). Isolation of neurotoxic peptides from the venom of the “armed” spider Phoneutria nigriventer. Toxicon 29:1225–1233.
Romano-Silva, M. A., Ribeiro, A. M., Ribeiro-Santos, R., Gomez, M. V., Diniz, C. R., Cordeiro M. N., and Brammer, M. J. (1993). Rat cortical synaptosomes have more than one mechanism for calcium entry linked to rapid glutamate release: Studies using the Phoneutria nigriventer toxin PhTx2 and potassium depolarization. Biochem. J. 269:313–319.
Schenberg, S., and Lima, F. A. (1966). Pharmacology of the polypeptides from the venom of the spider Phoneutria fera. Mem. Inst. Butantan. 33:627–638.
Schlegel,W., Winiger, B. P., Mollard, P., Vacher, P., Wuarin, F., Zahnd, G. R., Wollheim, C. B., and Dufy, B. (1987). Oscillation of cytosolic calcium in pituitary cells due to action potentials. Nature 329:719–721.
Souccar,C., Goncalo, M.C., Lapa, A. J., Troncone, L. R., Lebrun, I., Magnoli, F. (1995). Blockade of acetylcholine release at the motor endplate by a polypeptide from the venom of Phoneutria nigriventer. Br. J. Pharmacol. 116:2817–2823.
Troncone, L. R., Lebrun, I., Magnoli, F., and Yamane, T. (1995). Biochemical and pharmacological studies on a lethal neurotoxic polypeptide from Phoneutria nigriventer spider venom. Neurochem. Res. 20: 879–883.
Vieira, L. B., Kushmerick, C., Reis, H. J., Diniz, C. R., Cordeiro, M. N., Prado, M. A. M., Kalapothakis, E., Romano-Silva, M. A., and Gomez, M. V. (in press). PnTx3-6 a spider neurotoxin inhibits K+-evoked increase in intracellular calcium and calcium-dependent glutamate release in synaptosomes. Neuroch. Int.
Von Heijne, G. (1985). Signal sequences: The limits of variation. J. Mol. Biol. 184:99–105.
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Gomez, M.V., Kalapothakis, E., Guatimosim, C. et al. Phoneutria nigriventer Venom: A Cocktail of Toxins That Affect Ion Channels. Cell Mol Neurobiol 22, 579–588 (2002). https://doi.org/10.1023/A:1021836403433
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DOI: https://doi.org/10.1023/A:1021836403433