Tx2‐6 toxin from Phoneutria nigriventer spider improves relaxation induced by electrical stimulation of rat cavernosum strips

Background: Accidents involving the spider P. nigriventer are characterized by different symptoms including priapism. Some toxins from poisonous animals exert their toxic effects by modifying the properties of ion channels. We have previously demonstrated that Tx2‐6, a peptide extracted from the venom of P. nigriventer, improves erectile function in anesthetized rats. Here we investigated the mechanism involved in the Tx2‐6 potentiation of penile erection.Methods: Rat cavernosum strips were incubated with bretylium (3 x 10–5M) and contracted with phenylephrine (10–5 M). Relaxation responses were evoked by electrical field stimulation (EFS) or sodium nitroprusside (SNP) before and after 5 min incubation with Tx2–6 (10–8 M). The effect of Tx2‐6 on relaxation induced by EFS was also tested in the presence of atropine (10–6 M), conotoxin GVIA (10–6 M) or nifedipine (10–7 M).Results: Relaxation induced by SNP was not affected by Tx2‐6. EFS‐induced relaxation was significantly potentiated by Tx2‐6 and this effect was not affected by atropine, whereas blockade of N‐ or L‐Type Ca+2 channels abolished the potentiation of the relaxation induced by Tx2‐6.Conclusion: Tx2‐6 potentiates the relaxation of cavernosum tissue via Na+ and Ca+2 channels, facilitating the nitric oxide/cGMP pathway. Tx2‐6 has great potential for development of drugs to treat erectile dysfunction.SUPPORT: CNPq, FAPEMIG, NIH