Role of the extracellular cyclic AMP-adenosine pathway in the respiratory and neuromuscular physiology and physiopathology

• 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
• 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)

Scientific publications

(6)

(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)

MONTE, GABRIELA GUILHERME; NANI, V, JOAO; DE ALMEIDA CAMPOS, MARINA ROSSETO; DAL MAS, CAROLINE; NEGRI MARINS, LUCAS AUGUSTO; MARTINS, LUCAS GELAIN; TASIC, LJUBICA; MORI, MARCELO A.; HAYASHI, MIRIAN A. F.. Impact of nuclear distribution element genes in the typical and atypical antipsychotics effects on nematode Caenorhabditis elegans: Putative animal model for studying the pathways correlated to schizophrenia. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 92, p. 19-30, JUN 8 2019. (14/50867-3, 15/07019-4, 13/13392-4, 17/02413-1, 18/06510-4)

COELHO, PRISCILA DE O.; GUARNIER, FLAVIA A.; FIGUEIREDO, LEONARDO BRUNO; ZARAMELA, LIVIA S.; PACINI, ENIO S. A.; GODINHO, ROSELY O.; GOMES, MARCELO D.. Identification of potential target genes associated with the reversion of androgen-dependent skeletal muscle atrophy. Archives of Biochemistry and Biophysics, v. 663, p. 173-182, MAR 15 2019. (15/07019-4, 14/10898-7, 11/07487-7)

RODRIGUES, JULIANO Q. D.; CAMARA, HENRIQUE; JURKIEWICZ, ARON; GODINHO, ROSELY O.. Increased Gi protein signaling potentiates the negative chronotropic effect of adenosine in the SHR right atrium. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, v. 391, n. 5, p. 513-522, MAY 2018. (13/20402-6, 12/22763-3, 15/07019-4, 12/24828-5)

PACINI, ENIO S. A.; SANDERS-SILVEIRA, SARAH; GODINHO, ROSELY O.. The Extracellular cAMP-Adenosine Pathway in Airway Smooth Muscle. Journal of Pharmacology and Experimental Therapeutics, v. 366, n. 1, p. 75-83, JUL 1 2018. (15/07019-4)

DANTAS RODRIGUES, JULIANO QUINTELLA; CAMARA, HENRIQUE; DA SILVA JUNIOR, EDILSON DANTAS; GODINHO, ROSELY OLIVEIRA; JURKIEWICZ, ARON. Intrinsic Adaptation of SHR Right Atrium Reduces Heart Rate. Journal of Cardiovascular Pharmacology, v. 74, n. 6, p. 542-548, DEC 2019. (12/22763-3, 15/07019-4, 12/24828-5)

LIMA, SUNAMITA DE CARVALHO; PORTA, LUCAS DE CARVALHO; LIMA, ALVARO DA COSTA; CAMPEIRO, JOANA D'ARC; MEURER, YWLLIANE; TEIXEIRA, NATHALIA BERNARDES; DUARTE, THIAGO; OLIVEIRA, EDUARDO BRANDT; PICOLO, GISELE; GODINHO, ROSELY OLIVEIRA; et al. Pharmacological characterization of crotamine effects on mice hind limb paralysis employing both ex vivo and in vivo assays: Insights into the involvement of voltage-gated ion channels in the crotamine action on skeletal muscles. PLoS Neglected Tropical Diseases, v. 12, n. 8, AUG 2018. (13/13392-4, 15/07019-4, 17/02413-1)