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

• Grant number: 16/09539-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2016
• End date: May 31, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Autonomic Pharmacology
• Principal Investigator: Gilberto de Nucci
• Grantee: Alberto Fernando Oliveira Justo
• Host 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)

Scientific publications

(4)

(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. (17/15175-1, 16/09539-8)

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; et al. Endothelium modulates electrical field stimulation-induced contractions of Chelonoidis carbonaria aortic rings. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY, v. 233, JUL 2020. (18/24971-9, 16/04731-8, 16/09539-8)

LUCIANO AFONSO, PEDRO PAULO; AFONSO, MARIANA LUCIANO; BARBOSA, GABRIELA RODRIGUES; OLIVEIRA JUSTO, ALBERTO FERNANDO. Hospitalization due to mental and behavioral disorders caused by use of alcohol and psychoactive substances among older adults and elderly people in Brazil: a cross-sectional study. São Paulo Medical Journal, v. 140, n. 2, p. 8-pg., 2022-03-01. (16/09539-8)

JUSTO, ALBERTO FERNANDO O.; COLLACO, RITA DE CASSIA; LESCANO, CAROLINE HONAISER; DE OLIVEIRA, IVAN PIRES. Malignant neoplasm of breast in Brazilian women: A cross-sectional study from 2008 to 2019. JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, v. 115, n. 1, p. 8-pg., 2023-02-01. (17/02201-4, 17/26687-3, 16/09539-8)