Effect of sympathetic denervation on the rate of protein synthesis in rat skeletal muscle

• Published in: American journal of physiology: endocrinology and metabolism Vol. 286; no. 4; pp. E642 - E647
• Main Authors: Navegantes, Luiz Carlos C, Resano, Neusa M. Z, Baviera, Amanda M, Migliorini, Renato H, Kettelhut, Isis C
• Format: Journal Article
• Language: English
• Published: United States 01.04.2004
• Subjects: Adrenal Medulla - drug effects; Adrenal Medulla - metabolism; Adrenergic Agents - pharmacology; Adrenergic beta-Agonists - pharmacology; Animals; Blood Glucose - metabolism; Catecholamines - blood; Catecholamines - metabolism; Catecholamines - pharmacology; Clenbuterol - pharmacology; Corticosterone - blood; Fasting - metabolism; Guanethidine - pharmacology; Isoproterenol - pharmacology; Kinetics; Male; Muscle Proteins - biosynthesis; Muscle, Skeletal - drug effects; Muscle, Skeletal - innervation; Muscle, Skeletal - metabolism; Rats; Rats, Wistar; Sympathectomy; Tyrosine - metabolism
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00371.2003

Department of Physiology, Biochemistry and Immunology, School of Medicine, University of São Paulo, 14049-900 Ribeirão Preto, São Paulo, Brazil Submitted 18 August 2003 ; accepted in final form 28 November 2003 Rates of protein synthesis were investigated in skeletal muscles from rats submitted to chemical and surgical sympathectomy. Three models of sympathetic denervation were used: 1 ) treatment with guanethidine (100 mg·kg -1 ·day -1 sc); 2 ) lumbar sympathetic denervation (surgical excision of the second and third lumbar ganglia of the sympathetic chain, from which arises the postganglionic fibers to the skeletal muscles of rat hindlimb); and 3 ) adrenodemedullation. Protein synthesis was estimated in isolated soleus muscle by the rate of incorporation of [ 14 C]tyrosine (0.1 mM, 0.05 µCi/ml) into total protein. Soleus isolated after 2 and 4 days of chemical sympathectomy or after 3 days of lumbar denervation showed a 17-20% statistically significant decrease in in vitro rates of protein synthesis. These effects were reverted by addition of 10 -5 M isoproterenol or epinephrine in vitro. Neither clenbuterol nor isoproterenol (10 -7 , 10 -6 , or 10 -5 M) in vitro affected the rate of protein synthesis in soleus from normal rats. On the other hand, clenbuterol or epinephrine (10 -5 M) increased by 20% the rate of protein synthesis in soleus muscles from adrenodemedullated rats and prevented its decrease in muscles from fasted rats. The data suggest that the sympathetic nervous system stimulates protein synthesis in oxidative muscles, probably through the activation of 2 -adrenoceptors, especially in situations of hormonal or nutritional deficiency. catecholamines; isoproterenol; clenbuterol; surgical and chemical sympathectomy Address for reprint requests and other correspondence: I. C. Kettelhut, Dept. of Biochemistry, School of Medicine, USP, 14049-900 Ribeirão Preto, SP, Brazil (E-mail: idckette{at}fmrp.usp.br ).