Pharmacological and molecular study of scorpio toxins with relaxing action on the cavernous body

• Grant number: 00/10969-9
• Support Opportunities: Research Projects - Thematic Grants
• Start date: December 01, 2001
• End date: April 30, 2006
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Gilberto de Nucci
• Grantee: Gilberto de Nucci
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Scorpion venoms exert a variety of effects on excitable tissues, due to their action at the peripheral nervous system enhancing the release, of neurotransmitters. The clinical symptomatology observed in severe scorpion envenomation involves mainly sympathetic (tachycardia, hypertension, sweatíng and mydriasis) and parasympathetic (bradycardia, hypotension, secretions and miosis) stimulation as well as central manifestations such as irritabilíty, hyperthermia, vomiting, tremor and convulsion. The occurrence of priapism is also a common sign of scorpion envenomation. Nitric oxide released from NANC inhibitory nerve fibers has been shown to play a pivotal role in the neural mechanisms involved in penile erection. Nitric oxide has been identífied as an important inhibitory neurotransmitter of NANC relaxations in the penile corpus cavernosum of man, rabbit, dog, horse, monkey and mouse.We have shown that Androctonus australis and Buthotus judaicus scorpion venoms cause NO-dependent RbCC relaxations. Both AAV and BJV relax the cavernosal tissues by activating NANC nerve fibres with subsequent release of NO that in turn lead to relaxation through activation of soluble guanylate, cyclase and hence, cyclic GMP formation. The non-selective NO synthase inhibitor L-NAME (but not its inactive enantiomer D-NAME) significantly reduced the venom-induced relaxations. The reduction by L-NAME was partially reversed by the NO precursor L-arginine (but not D-arginine), thus confirming the involvement of NO in the relaxant responses elicited by both AAV and BJV... (AU)