Studies in rats and mice on the toxin Tx2-6 from the spider Phoneutria nigriventer that induces priapism

• Grant number: 16/19824-1
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): January 01, 2017
• Effective date (End): December 31, 2017
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal researcher: Lanfranco Ranieri Paolo Troncone
• Grantee: Caroline Martins Dominguez
• Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The Present investigation is intended to better understand the molecular mechanisms involved in priapism induced by the spider toxins Tx2-6 and Tx2-5 found in the venom of the spider Phoneutria nigriventer. This spider venom contains a large number of toxins with diverse pharmacological actions. The Tx2-5 and Tx2-6 were identified in this laboratory as responsible for the priapism and are among the most toxic compounds of this venom. We described the involvement of NO in this process and discarded the involvement of CNS, as well as we described the systemic vascular congestion that culminates by death caused by respiratory collapse. Also gene expression alterations in penile tissue, related to the NO signaling cascade revealed several genes affected and by bioinformatics tools a potential endothelin receptor was involved. Nonetheless, the ultimate molecular mechanism of toxin-induced priapism is unknown, since other toxins that affect sodium channel inactivation do not induce priapism. Therefore, we intend to investigate the molecular mechanism by pharmacological manipulations and recordings of intra-cavernosal pressure in rats and mice. This project represents a development of this important investigation and can potentially lead to the proposal of new alternatives in the management of impotence and erectile function as well as priapism, which is a medical emergency. (AU)