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

Grant number: 16/09539-8
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): September 01, 2016
Effective date (End): May 31, 2020
Field of knowledge:Biological Sciences - Pharmacology - Autonomic Pharmacology
Principal researcher:Gilberto de Nucci
Grantee:Alberto Fernando Oliveira Justo
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated scholarship(s):18/10414-0 - Study of the regulation of eNOS Tyr81 phosphorylation, BE.EP.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 3Hacetylcholine 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)

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Scientific publications
(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)
JUSTO, ALBERTO FERNANDO O.; DE OLIVEIRA, MARIANA G.; CALMASINI, FABIANO B.; ALEXANDRE, EDUARDO C.; BERTOLLOTTO, GABRIELA MARIA; JACINTHO, FELIPE FERNANDES; ANTUNES, EDSON; MONICA, FABIOLA Z. Preserved activity of soluble guanylate cyclase (sGC) in iliac artery from middle-aged rats: Role of sGC modulators. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 106, p. 9-16, JAN 1 2021. Web of Science Citations: 0.
CAMPOS, RAFAEL; JACINTHO, FELIPE FERNANDES; BRITTO-JUNIOR, JOSE; MONICA, FABIOLA Z.; OLIVEIRA JUSTO, ALBERTO FERNANDO; PUPO, ANDRE SAMPAIO; MORENO, RONILSON AGNALDO; DE SOUZA, VALERIA BARBOSA; SCHENKA, ANDRE ALMEIDA; ANTUNES, EDSON; DE NUCCI, GILBERTO. Endothelium modulates electrical field stimulation-induced contractions of Chelonoidis carbonaria aortic rings. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY, v. 233, JUL 2020. Web of Science Citations: 0.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.