Sato Shogo, Nomura Sachiko, Kawano Fuuun, Tanihata Jun, Tachiyashiki Kaoru, Imaizumi Kazuhiko
Laboratory of Physiological Sciences, Faculty of Human Sciences, Waseda University, Tokorozawa, Saitama, Japan.
J Pharmacol Sci. 2008 Aug;107(4):393-400. doi: 10.1254/jphs.08097fp. Epub 2008 Aug 2.
The beta2-agonist clenbuterol [4-amino-alpha(t-butyl-amino)methyl-3,5-dichlorobenzyl alcohol] is used as a non-steroidal anabolic drug for sports doping. The effects of clenbuterol on the transcriptional process and mRNA stability of beta-adrenoceptor (beta-AR) in skeletal and cardiac muscles are still unknown. Therefore, we investigated the effects of clenbuterol on beta1- and beta2-AR mRNA expressions of fast-twitch fiber-rich extensor digitorum longus (EDL), slow-twitch fiber-rich soleus (SOL), and left ventricle (LV) muscles by real-time RT-PCR. Adult male Sprague Dawley rats were divided into the clenbuterol-administered group and control group. The administration (dose = 1.0 mg/kg body weight/day, s.c.) of clenbuterol was maintained for 10 days. The administration of clenbuterol significantly increased the weight, RNA concentration, and total RNA content of EDL muscle. No effects of clenbuterol on those of SOL and LV muscles, however, were observed. The administration of clenbuterol significantly decreased beta1-AR mRNA expression of LV muscle. Furthermore, the administration of clenbuterol significantly decreased beta2-AR mRNA expression of EDL and LV muscles. No effect of clenbuterol on beta2-AR mRNA expression of SOL muscle, however, was observed. These results suggest that the effects of clenbuterol on beta1- and beta2-AR mRNA expressions and muscle hypertrophy depend on muscle fiber types.
β2激动剂克仑特罗[4-氨基-α(叔丁基氨基)甲基-3,5-二氯苄醇]被用作体育兴奋剂中的非甾体类同化药物。克仑特罗对骨骼肌和心肌中β肾上腺素能受体(β-AR)转录过程及mRNA稳定性的影响尚不清楚。因此,我们通过实时逆转录聚合酶链反应研究了克仑特罗对富含快肌纤维的趾长伸肌(EDL)、富含慢肌纤维的比目鱼肌(SOL)和左心室(LV)肌肉中β1-和β2-AR mRNA表达的影响。成年雄性Sprague Dawley大鼠被分为克仑特罗给药组和对照组。克仑特罗的给药(剂量=1.0mg/kg体重/天,皮下注射)持续10天。克仑特罗给药显著增加了EDL肌肉的重量、RNA浓度和总RNA含量。然而,未观察到克仑特罗对SOL和LV肌肉的这些指标有影响。克仑特罗给药显著降低了LV肌肉中β1-AR mRNA的表达。此外,克仑特罗给药显著降低了EDL和LV肌肉中β2-AR mRNA的表达。然而,未观察到克仑特罗对SOL肌肉中β2-AR mRNA表达有影响。这些结果表明,克仑特罗对β1-和β2-AR mRNA表达及肌肉肥大的影响取决于肌纤维类型。