Blockade of neuronal nitric oxide synthase abolishes the toxic effects of Tx2-5, a lethal Phoneutria nigriventer spider toxin.

Abstract

The primary goal of this study was to determine whether Tx2-5, a sodium channel selective toxin obtained from the venom of the spider Phoneutria nigriventer, produced penile erection by means of nitric oxide mechanism. Toxin identity was analyzed by MALDI-TOF, ES-MS and N-terminal amino acid sequencing. Pretreating mice with the non-selective nitric oxide synthase (NOS) inhibitor N(omega)-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and the selective neuronal-NOS inhibitor 7-Nitroindazole (7-NI) prior to Tx2-5 i.p. (10 microg/25 g mouse) injection challenged the hypothesis above. Controls were injected with the D-isomer or DMSO or saline. Results demonstrated that L-NAME inhibited penile erections in about half the animals treated, while 7-NI completely abolished this effect. Interestingly 7-NI also abolished all the other symptoms of intoxication induced by Tx2-5, including salivation, respiratory distress and death. Tx2-5 killed all the animals of the control group and no one in the 7-NI-treated group. We conclude that (1) intraperitoneal injections of Tx2-5 induce a toxic syndrome that include penile erection, hypersalivation and death by respiratory distress or pulmonary edema; (2) pretreatment with the non-selective NOS inhibitor L-NAME reduces the penile erection and partially protects from the lethal effects of Tx2-5; (3) pretreatment with the nNOS-selective inhibitor 7-NI completely abolishes all the toxic effects of Tx2-5, including penile erection and death suggesting that nNOS is the major player in this intoxication; (4) toxins from other animals that affect sodium channels in the same way as Tx2-5 and induce similar toxic syndromes may have as a major common target, the activation of nitric oxide synthases.

• Authors: C M Yonamine, L R P Troncone, M A P Camillo
• Journal: Toxicon : official journal of the International Society on Toxinology (Toxicon) Vol. 44 Issue 2 Pg. 169-72 (Aug 2004) ISSN: 0041-0101 [Print] England
• PMID: 15246765 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Enzyme Inhibitors
• Indazoles
• Neuropeptides
• Neurotoxins
• Spider Venoms
• Tx2 neurotoxin
• 7-nitroindazole
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type I
• Nos1 protein, mouse
• NG-Nitroarginine Methyl Ester

Topics

• Analysis of Variance
• Animals
• Enzyme Inhibitors (pharmacology)
• Indazoles (pharmacology)
• Lung Diseases (chemically induced, enzymology)
• Male
• Mice
• Mice, Inbred BALB C
• NG-Nitroarginine Methyl Ester (pharmacology)
• Neuropeptides (toxicity)
• Neurotoxins (toxicity)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Nitric Oxide Synthase Type I
• Priapism (chemically induced, enzymology)
• Spider Venoms (toxicity)
• Spiders