| Grant number: | 15/07019-4 |
| Support Opportunities: | Regular Research Grants |
| Start date: | September 01, 2015 |
| End date: | February 28, 2018 |
| 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 |
| City of the host institution: | São Paulo |
| Associated researchers: | Enio Setsuo Arakaki Pacini |
Abstract
In the skeletal muscle, the intracellular cyclic AMP (cAMP) regulates several processes including muscle contraction, metabolism, and synaptic protein expression. Previous studies from our lab have shown that increment in cAMP production induced by activation of stimulatory (Gs) protein coupled receptor (GsPCR) or adenylyl cyclase is followed by efflux of this cyclic nucleotide (Godinho and Costa-Jr, 2003). Once outside the cell, cAMP exerts its effects via its metabolite adenosine, generated by sequential action of ecto-phosphodiesterases and ecto-5'-nucleotidases (Chiavegatti et al., 2008). Recently, our group showed that the extracellular cAMP-adenosine pathway modulates skeletal muscle contraction, being responsible for indirect coupling of ²2 adrenoceptors to inhibitory G (Gi) protein (Duarte et al., 2012) . An ongoing research project in our lab focuses on pharmacological strategies for attenuation of skeletal muscle atrophy associated with pathological conditions (e.g., cancer, diabetes, and renal failure). Taking into account a) the cytoprotective effect of adenosine on skeletal muscle; b) the positive correlation between muscle injury and activation of proteolytic systems and c) the antiproteolytic action of adenosine, we will evaluate the role of the extracellular cAMP-adenosine pathway on the regulation skeletal muscle proteolysis. In addition, taking into account the involvement of cAMP on the relaxation of bronchiolar smooth muscle induced by catecholamines or ²2 adrenoceptor agonists used for treatment of pulmonary obstructive chronic diseases, we will also evaluate the contribution of extracellular cAMP-adenosine pathway on the reactivity of tracheal smooth muscle and on pathophysiology of the respiratory tract from normal and sensitized by ovalbumin. (AU)
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