Effects of β₂-Agonist, Clenbuterol on β₂-Adrenoceptor mRNA Expression and the Regulatory Factors in rat Skeletal and Left Ventricle Muscles

 

Shogo Sato

Graduate School of Human Sciences, Waseda University, 2-579-15 Mikajima, Tokorozawa, 359-1192, Japan

 

β₂-agonist, clenbuterol [CLE: 4-amino-a (t-butyl-amino) methyl-3, 5-dichlorobenzyl alcohol] is used as a non-steroidal anabolic drug for sports doping. Recently, we reported that the effects of CLE on β₁- and β₂-adrenoceptor (AR) mRNA expressions in skeletal and cardiac muscles depend on muscle fiber types (Sato S, et al.: J Pharmacol Sci, 107:393-400, 2008). Next, the effects of CLE-administration (dose=1.0 mg/kg BW/day, for 10 days, s.c.) on the mRNA expressions of transcription regulatory factors and post-transcription regulatory factors of β₁- and β₂-AR mRNA expressions in fast-twitch fiber rich extensor digitorum longus (EDL) and plantaris (PLA), slow-twitch fiber rich soleus (SOL), and left ventricle (LV) by real-time RT-PCR were studied in adult male rats. CLE significantly decreased the mRNA expression of transcription regulatory factor, glucocorticoid receptor (GR) and post-transcription regulatory factors in EDL, without changing those in SOL and LV. However, no effects of CLE on transcription regulatory factor, cAMP response element binding protein (CREB) were observed in these muscles. These results suggest that muscle fiber type dependent effects of CLE on β₂-AR mRNA expression are closely related to the reduction of transcription regulatory factor, GR levels.

 

Key words: clenbuterol, β₂-adrenoceptor, glucocorticoid receptor