Nitric oxide release from human corpus cavernosum induced by a purified scorpion toxin

Abstract

Objectives: To investigate the effects of a purified scorpion toxin (Ts3) on human corpus cavernosum (HCC) in vitro. Scorpion venoms cause a massive release of neurotransmitters that contribute to the clinical symptoms resulting from envenomation.

Methods: HCC strips were mounted in organ baths containing Krebs solution. After equilibration, the tissues were precontracted with phenylephrine (10 micromol/L). The relaxations caused by Ts3 (30 nmol/L) were compared with those induced by electrical field stimulation (1 to 20 Hz) and nitric oxide (NO, 1 to 100 micromol/L).

Results: The addition of Ts3 evoked long-lasting relaxations of precontracted HCC strips, and exogenously applied NO and electrical field stimulation caused short-lived responses. The NO synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 micromol/L) reduced by 87% +/- 2% the Ts3-induced relaxations; this inhibition was reversed by pretreating the tissues with L-arginine (1 mmol/L). The relaxant responses mediated by Ts3 were blocked to a similar degree by the soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3,-alquinoxalin-1-one] (10 micromol/L). In contrast, the addition of the phosphodiesterase type 5 inhibitor sildenafil (0.1 micromol/L) significantly enhanced Ts3-evoked relaxations by 78% +/- 4%. The sodium channel blocker tetrodotoxin (1 micromol/L) completely blocked the relaxant responses elicited by both Ts3 and electrical field stimulation, without significantly affecting those elicited by NO.

Conclusions: The results indicate that Ts3 relaxes the HCC through the release of NO from nitrergic nerves. The elucidation of this mechanism is useful for the development of new therapeutic strategies to treat priapism after scorpion envenomation or to modulate sodium channel activity in the case of penile dysfunction.