Recombinant Phoneutria nigriventer Delta-ctenitoxin-Pn2a

Toxin that is known to potentiate erectile function. It binds voltage-dependently to sodium channels (Nav), inhibits the inactivation of the activated channels and decreases the peak inward current. The toxin delays inactivation of Nav1.2/SCN2A, Nav1.3/SCN3A, Nav1.4/SCN4A and Nav1.8/SCN10A, slows the inactivation process and decreases the sodium peak amplitude of Nav1.5/SCN5A and Nav1.6/SCN8A. In vivo, it enhances erectile function by inducing the release of nictric oxide (NO): it slows the sodium current, leading to depolarization, which leads to an increase in calcium influx (probably via activation of N-type calcium channels) which in turn activates neuronal NO synthase (nNOS/NOS1), inducing nitric oxide (NO) production. In a final step, NO activates soluble guanylate cyclase (GUCY1A1/GUCY1B1) which in turn increases cGMP formation, resulting in penile erection. It is noteworthy that the toxin does not provoke erection by inhibiting phosphodiesterase type 5 (PDE5A), an enzyme that hydrolysis cGMP. In vivo, it also causes scratching, lacrimation, hypersalivation, sweating and agitation followed by spastic paralysis of the anterior and posterior extremities and death at dose levels of 0.79 mg/mouse. It is insecticidal to the larval and adult forms of the house fly. The toxin also improves cavernosal relaxation in different models where erectile dysfonction is observed, such as deoxycorticosterone-acetate (DOCA)-salt hypertensive rats, mice models for type-1 diabetes, as well as elderly rats.