Involvement of cyclic AMP and extracellular calcium on the excitation-contraction coupling and on the maintainance of skeletal muscle mass

• Grant number: 11/01519-4
• Support Opportunities: Regular Research Grants
• Duration: April 01, 2012 - September 30, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Rosely Oliveira Godinho
• Grantee: Rosely Oliveira Godinho
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Muscle wasting and weakness are associated to many diseases and conditions including aging, cancer cachexia and neuromuscular dysfunctions, which usually involves continued muscle protein breakdown resulting in muscle atrophy. Therapeutic strategies for attenuating muscle wasting and improving muscle function vary in efficacy. Exercise and pharmacological intervention with anabolic drugs are able to slow the rate of muscle atrophy in some muscle wasting conditions, but in most cases they cannot halt or reverse the wasting process. More recently, ²2-adrenoceptor agonists have been shown to exert significant anabolic actions on skeletal muscle, via activation of adenylyl cyclase and increment of intracellular cAMP levels. Unpublished results of our lab suggest the involvement of Ca2+-sensitive AC inhibited by extracellular Ca2+ on attenuation of muscle proteolysis and weakness. The aim of this project is evaluate the possible cross talk between GsPCR/AC/cAMP and Ca2+ signaling pathways and electromechanical activity in the maintenance of muscle mass and strength by studying the combined effect of exercise/electromechanical activity, GsPCR agonists and L-type channel antagonists on muscle proteolysis and contraction force. This study is intended to provide new therapeutic strategies to potentially attenuate muscle atrophy and improve muscle function, which will ultimately lead to improvement in the quality of life for affected patients. (AU)

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)

MENEZES-RODRIGUES, FRANCISCO SANDRO; PIRES-OLIVEIRA, MARCELO; DUARTE, THIAGO; PAREDES-GAMERO, EDGAR JULIAN; CHIAVEGATTI, TIAGO; GODINHO, ROSELY OLIVEIRA. Calcium influx through L-type channels attenuates skeletal muscle contraction via inhibition of adenylyl cyclases. European Journal of Pharmacology, v. 720, n. 1-3, p. 326-334, NOV 15 2013. (11/01519-4)