Decreased monocarboxylate transporter 1 in rat soleus and EDL muscles exposed to clenbuterol

Abstract

We hypothesized that a shift in muscle fiber type induced by clenbuterol would change monocarboxylate transporter 1 (MCT1) content and activity of lactate dehydrogenase (LDH) and isoform pattern and shift myosin heavy chain (MHC) pattern in soleus (Sol) and extensor digitorum longus (EDL) of male rats. In the clenbuterol-administered rats (2.0 mg x kg(-1) x day(-1) subcutaneously for 4 wk), the ratio of muscle weight to body weight increased in the Sol (P < 0.05) and the EDL (P < 0.01). Clenbuterol induced the appearance of fast MHC(2D) and decreased slow MHC(1) in Sol (13%) but had no effect on EDL. The MHC pattern of Sol changed from slow to fast type. Clenbuterol increased LDH-specific activity (P < 0.01) and the ratio of the muscle-type isozyme of LDH to the heart type (P < 0.05) in Sol. The LDH total activity of the EDL muscle was also increased (P < 0.05). Furthermore, MCT1 content significantly (P < 0.05) decreased in both Sol and EDL (27 and 52%, respectively). This study suggests that clenbuterol might mediate the shift of MHC from slow to fast type and the changes in the regulation of lactate metabolism. Novel to this study is the observation that clenbuterol decreases MCT1 content in the hindlimb muscles and that the decrease in MCT1 is not muscle-type specific. It may suggest that the genetic expressions of individual factors involving slow-type MHC, heart-type isozyme of LDH, and MCT1 are associated with one another but are regulated independently.

Effects of the β2-Agonist Clenbuterol on β1- and β2-Adrenoceptor mRNA Expressions of Rat Skeletal and Left Ventricle Muscles

“…It is well known that β 2 -agonists increase the crosssectional area of fast-twitch fibers (4,6,7,25). In addition, the effects of β 2 -agonists on the functional properties of skeletal muscles may be associated with the metabolic responses (7,14,25,36).…”

“…In addition, the effects of β 2 -agonists on the functional properties of skeletal muscles may be associated with the metabolic responses (7,14,25,36). Kitaura et al (25) reported that clenbuterol induced a transition from slow to fast myosin heavy chain (MHC) phenotypes of SOL muscle, but no significant changes in MHCs of EDL muscle. Furthermore, they also reported that Up arrow: significantly higher in the clenbuterol-administered group than in the control group, down arrow: significantly lower in the clenbuterol-administered group than in the control group, n.s.…”

“…clenbuterol decreased monocarboxylate transporter 1 content in EDL and SOL muscles, increased lactate dehydrogenase (LDH) total activity in EDL muscle, and increased LDH-specific activity and the ratio of the muscle-type isozyme of LDH (anaerobic activity) to the heart-type (aerobic activity) in SOL muscle (25). Additionally, clenbuterol-induced shift of the metabolic property from oxidative to glycolytic in SOL muscle is demonstrated by the increase in phosphofructokinase activity and decrease in citrate synthase activity (36).…”

“…The proportion of these muscle fibers is different in each skeletal muscle. Extensor digitorum longus (EDL) and soleus (SOL) muscles are known as a typical fast-twitch fiber-rich and a slow-twitch fiber-rich muscle, respectively, in rats (7,25). These muscle fibers are different in the velocity of contraction, metabolic properties, and β-AR distributions (4,7,14,15,25).…”

“…Extensor digitorum longus (EDL) and soleus (SOL) muscles are known as a typical fast-twitch fiber-rich and a slow-twitch fiber-rich muscle, respectively, in rats (7,25). These muscle fibers are different in the velocity of contraction, metabolic properties, and β-AR distributions (4,7,14,15,25). Jensen et al (26,27) reported that the β 2 -AR subtype was contained in about 80% -95% of total β-ARs in skeletal muscles and relatively higher in the slow-twitch fiber-rich SOL muscle than in the fast-twitch fiber-rich EDL muscle.…”