title: CL 316,243, a selective beta3-adrenergic agonist, inhibits protein breakdown in rat skeletal muscle.
abstract: The in vitro effect of CL 316,243 (CL), a selective beta3-adrenoceptor agonist in the rate of overall proteolysis, the activity of proteolytic systems (lysosomal, Ca2+-dependent, ATP-dependent, and ATP-independent) and in the process of protein synthesis was investigated in rat skeletal muscles. The rate of overall proteolysis in soleus muscle from rats incubated with CL (10(-4) and 10(-5) M) or epinephrine (10(-5) M) was significantly decreased. In vitro rates of maximal activity of Ca2+-dependent proteolysis in soleus muscles were decreased by about 41% in the presence of 10(-5) M CL. No change was observed in the activities of the lysosomal, ATP-dependent or ATP-independent proteolytic systems. The anti-proteolytic effect of CL or epinephrine was partially prevented by 10(-5) M SR 59230A, a selective beta3-adrenoceptor antagonist. The increase of proteolysis induced by food deprivation in soleus was abolished by in vitro addition of 10(-5) M CL. No change in proteolysis was observed in extensor digitorum longus (EDL) muscles incubated with any concentration of the beta3-adrenoceptor agonist tested. Rates of protein synthesis were not affected by 10(-4) M CL neither in soleus nor EDL. The data suggest that a beta3-adrenoceptor-mediated inhibition of Ca2+-dependent proteolysis participates of the antiproteolytic effect of catecholamines in oxidative muscles.
authors.affiliation: Department of Physiology, Biochemistry and Immunology, School of Medicine, University of São Paulo, 14049-900, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Luiz Carlos C
authors.initials: LC
authors.lastname: Navegantes
authors.forename: Neusa M Z
authors.initials: NM
authors.lastname: Resano
authors.forename: Amanda Martins
authors.initials: AM
authors.lastname: Baviera
authors.forename: Renato H
authors.initials: RH
authors.lastname: Migliorini
authors.forename: Isis C
authors.initials: IC
authors.lastname: Kettelhut
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002976:Clenbuterol / Q000494:pharmacology; D004149:Dioxoles / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D005215:Fasting / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000318:Adrenergic beta-Agonists; D004149:Dioxoles; D009124:Muscle Proteins; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D002976:Clenbuterol; D004837:Epinephrine