title: Clenbuterol antagonizes glucocorticoid-induced atrophy and fibre type transformation in mice.
abstract: Beta-agonists and glucocorticoids are frequently coprescribed for chronic asthma treatment. In this study the effects of 4 week treatment with beta-agonist clenbuterol (CL) and glucocorticoid dexamethasone (DEX) on respiratory (diaphragm and parasternal) and limb (soleus and tibialis) muscles of the mouse were studied. Myosin heavy chain (MHC) distribution, fibres cross sectional area (CSA), glycolytic (phosphofructokinase, PFK; lactate dehydrogenase, LDH) and oxidative enzyme (citrate synthase, CS; cytochrome oxidase, COX) activities were determined. Muscle samples were obtained from four groups of adult C57/B16 mice: (1) Control (2) Mice receiving CL (CL, 1.5 mg kg(-1) day(-1) in drinking water) (3) Mice receiving DEX (DEX, 5.7 mg kg(-1) day(-1) s.c.) (4) Mice receiving both treatments (DEX + CL). As a general rule, CL and DEX showed opposite effects on CSA, MHC distribution, glycolytic and mitochondrial enzyme activities: CL alone stimulated a slow-to-fast transition of MHCs, an increase of PFK and LDH and an increase of muscle weight and fibre CSA; DEX produced an opposite (fast-to-slow transition) change of MHC distribution, a decrease of muscle weight and fibre CSA and in some case an increase of CS. The response varied from muscle to muscle with mixed muscles, as soleus and diaphragm, being more responsive than fast muscles, as tibialis and parasternal. In combined treatments (DEX + CL), the changes induced by DEX or CL alone were generally minimized: in soleus, however, the effects of CL predominated over those of DEX, whereas in diaphragm DEX prevailed over CL. Taken together the results suggest that CL might counteract the unwanted effects on skeletal muscles of chronic treatment with glucocorticoids.
authors.affiliation: Department of Experimental Medicine, Human Physiology Unit, University of Pavia, 27100 Pavia, Italy. map@unipv.it
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Pellegrino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D'Antona
authors.forename: Susan
authors.initials: S
authors.lastname: Bortolotto
authors.forename: Federica
authors.initials: F
authors.lastname: Boschi
authors.forename: Ornella
authors.initials: O
authors.lastname: Pastoris
authors.forename: Roberto
authors.initials: R
authors.lastname: Bottinelli
authors.forename: Biagio
authors.initials: B
authors.lastname: Polla
authors.forename: Carlo
authors.initials: C
authors.lastname: Reggiani
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001284:Atrophy; D002976:Clenbuterol / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D003964:Diaphragm / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology*; D004347:Drug Interactions; D005938:Glucocorticoids / Q000494:pharmacology*; D007150:Immunohistochemistry; D007536:Isomerism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; D005938:Glucocorticoids; D003907:Dexamethasone; D018995:Myosin Heavy Chains; D002976:Clenbuterol