Because most of the toxins from arthropod venoms are active on ion channels, they may directly or indirectly evoke changes in cell physiology. Such alterations may include release or inhibition CHIR-99021 mw of neurotransmitters and enzyme activation. Some arthropod toxins have been claimed to promote cavernosal relaxation and improve erectile function. As a result, the action of these toxins in CC leads to NO release, as shown by various authors (Teixeira et al., 2004a and Teixeira et al., 2004b; Yonamine et al., 2004;
Nunes et al., 2008). However, the mechanisms by which these toxins enhance penile erection have not been completely elucidated. The first related observation of priapism, following the injection
of venoms from spiders of the genus Phoneutria, seems to have been made in dogs ( Schenberg and Pereira-Lima, 1962). Nevertheless, priapism has been frequently observed in accidents involving men mostly the youngs. In vitro experiments showed that P. nigriventer venom was able to relax rabbit CC ( Lopes-Martins et al., 1994). Other studies have highlighted fractions or peptides (i.e. PNV2, PNV4) isolated from this venom as active in erectile function ( Bento et al., 1993; Rego et al., 1996). In the last find more decade, two toxins derived from PhTx2 fraction, PnTx2-5 and PnTx2-6, initially purified and characterized by the group of C.R. Diniz (Cordeiro et al., 1992), were identified as PRKD3 directly responsible for priapism symptoms (Yonamine et al., 2004; Nunes et al., 2008). The toxins PnTx2-6 and PnTx2-5 (Pn of P. nigriventer) have also been called Tx2-6 and Tx2-5, respectively, in the literature. So, the use of both terms is correspondent. Both toxins are very similar
in primary sequence (approximately 89% similarity, Fig. 3B) and have clearly shown a delay in the fast inactivation of voltage-dependent Na+ channels ( Araujo et al., 1993; Matavel et al., 2009). Biodistribution studies using labeled PnTx2-6 in mice found significantly higher toxin levels in testicles ( Yonamine et al., 2004) and penis ( Nunes et al., 2010) when compared to other tissues, after intraperitoneal injection of the toxin. It was also demonstrated that the priapism caused by intraperitoneal injection of PnTx2-5 in mice was prevented by pre-treatment with a specific or non-specific NOS inhibitor, 7NI and L-NAME, respectively ( Yonamine et al., 2004). The authors suggested that the toxin could be involved in neuronal depolarization in penis, based on previous observations showing that this toxin slowed down the fast inactivation of Na+ channels ( Araujo et al., 1993). In addition, priapism was also observed by direct injection of PnTx2-6 into mice CC ( Andrade et al., 2008). A microarray study analyzing differential gene expression of the NO pathway in mice erectile tissue before and after PnTx2-6 treatment shown that 10.
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