Pharmacological, eletrophysiological and morphological characterization of a novel TTX-resistant sodium channel coupled to corpus cavernosum of snakes

• Grant number: 11/11828-4
• Support Opportunities: Research Projects - Thematic Grants
• Start date: September 01, 2012
• End date: February 28, 2017
• Field of knowledge: Biological Sciences - Pharmacology - Autonomic 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
• Pesquisadores principais: Antonio Carlos Cassola ; Edson Antunes
• Associated researchers: Konradin Metze
• Associated scholarship(s): 15/15583-7 - Pharmacological, eletrophysiological and morphological characterization of novel tetrodotoxin-resistant sodium channel coupled to corpus cavernosum of snakes, BP.DD; 14/07762-6 - Immunohistochemical and morphological study of Crotalus durissus terrificus, Epicrates cenchria and Boa constrictor hemipenis, BP.PD; 13/04994-0 - Smooth muscle contraction mechanisms of Epicrates chencria and Boa constrictor, BP.DD

Abstract

Corpora cavernosa from humans and other mammals relax to transmural stimulation, and these relaxations are sensitive to voltage-gated sodium channel blockers such as tetrodotoxin (TTX). Snakes and lizards are unique among amniote vertebrates in having a bilaterally symmetrical intromitteny penis, known as hemipenises. The transmural stimulation of Crotalus durissus terrificus hemipenises causes relaxation which is insensitive to TTX, indicating the presence of a novel sodium channel. The objective of this project is to perform a complete study of this channel, since this may offer a new insight as a potential therapeutical target for erectile dysfunction and other diseases. This will be accomplished with the following steps: * Cloning of this sodium channel and expression in Xenopus oocytes to perform full electrophysiological studies. * Pharmacological study using bioassay and release of 3H-noradrenaline and 3H-acetylcholine of the Crotalus durissus terrificus hemipenises. * Morphological localization using transmission electron microscopy of the novel sodium channel. * Screening of new toxins isolated from Conus striatus and Conus sp as potential inhibitors of this novel sodium channel. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CAMPOS, RAFAEL; OLIVEIRA JUSTO, ALBERTO FERNANDO; JACINTHO, FELIPE FERNANDES; MONICA, FABIOLA Z.; ROJAS-MOSCOSO, JULIO ALEJANDRO; MORENO, RONILSON AGNALDO; NAPOLITANO, MAURO; COGO, JOSE CARLOS; DE NUCCI, GILBERTO. Pharmacological and transcriptomic characterization of the nitric oxide pathway in aortic rings isolated from the tortoise Chelonoidis carbonaria. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY, v. 222, p. 82-89, AUG 2019. (11/11828-4)

CAMPOS, RAFAEL; MONICA, FABIOLA Z.; RODRIGUES, RENATA LOPES; ROJAS-MOSCOSO, JULIO ALEJANDRO; MORENO, RONILSON AGNALDO; COGO, JOSE CARLOS; DE OLIVEIRA, MARCO ANTONIO; ANTUNES, EDSON; DE NUCCI, GILBERTO. Tetrodotoxin-insensitive electrical field stimulation-induced contractions on Crotalus durissus terrificus corpus cavernosum. PLoS One, v. 12, n. 8, AUG 24 2017. (11/11828-4)

PORTO, MARCOVAN; DE OLIVEIRA, MARCO ANTONIO; PISSINATTI, LORENZO; RODRIGUES, RENATA LOPES; ROJAS-MOSCOSO, JULIO ALEJANDRO; COGO, JOSE CARLOS; METZE, KONRADIN; ANTUNES, EDSON; NAHOUM, CESAR; MONICA, FABIOLA Z.; et al. The Evolutionary Implications of Hemipenial Morphology of Rattlesnake Crotalus durissus terrificus (Laurent, 1768) (Serpentes: Viperidae: Crotalinae). PLoS One, v. 8, n. 6, JUN 26 2013. (11/11828-4)

CAMPOS, RAFAEL; OLIVEIRA JUSTO, ALBERTO FERNANDO; MONICA, FABIOLA Z.; COGO, JOSE CARLOS; MORENO, RONILSON AGNALDO; DE SOUZA, VALERIA BARBOSA; SCHENKA, ANDRE ALMEIDA; DE NUCCI, GILBERTO. Electrical field-induced contractions on Crotalus durissus terrificus and Bothrops jararaca aortae are caused by endothelium-derived catecholamine. PLoS One, v. 13, n. 9, SEP 10 2018. (11/11828-4)

CAMPOS, RAFAEL; MONICA, FABIOLA Z.; OLIVEIRA JUSTO, ALBERTO FERNANDO; COGO, JOSE CARLOS; OLIVEIRA, EDVANA DE TOLEDO; MORENO, RONILSON AGNALDO; ANTUNES, EDSON; DE NUCCI, GILBERTO. Electrical field stimulation-induced contractions on Pantherophis guttatus corpora cavernosa and aortae. PLoS One, v. 13, n. 4, APR 19 2018. (11/11828-4)