Skeletal muscle myosin heavy chain isoforms and energy metabolism after clenbuterol treatment in the rat.
Prolonged treatment with the beta(2)-adrenoceptor agonist clenbuterol (1-2 mg. kg body mass(-1). day (-1)) is known to induce the hypertrophy of fast-contracting fibers and the conversion of slow- to fast-contracting fibers. We investigated the effects of administering a lower dose of clenbuterol (250 microgram. kg body mass(-1). day (-1)) on skeletal muscle myosin heavy chain (MyHC) protein isoform content and adenine nucleotide (ATP, ADP, and AMP) concentrations. Male Wistar rats were administered clenbuterol (n = 8) or saline (n = 6) subcutaneously for 8 wk, after which the extensor digitorum longus (EDL) and soleus muscles were removed. We demonstrated an increase of type IIa MyHC protein content in the soleus from approximately 0.5% in controls to approximately 18% after clenbuterol treatment (P < 0.05), which was accompanied by an increase in the total adenine nucleotide pool (TAN; approximately 19%, P < 0.05) and energy charge [E-C = (ATP + 0.5 ADP)/(ATP + ADP + AMP); approximately 4%; P < 0.05]. In the EDL, a reduction in the content of the less prevalent type I MyHC protein from approximately 3% in controls to 0% after clenbuterol treatment (P < 0.05) occurred without any alterations in TAN and E-C. These findings demonstrate that the phenotypic changes previously observed in slow muscle after clenbuterol administration at 1-2 mg. kg body mass(-1). day(-1) are also observed at a substantially lower dose and are paralleled by concomitant changes in cellular energy metabolism.
Rajab
P
P
School of Biomedical Sciences, University Medical School, Queen's Medical Center, Nottingham NG7 2UH, United Kingdom.
Fox
J
J
Riaz
S
S
Tomlinson
D
D
Ball
D
D
Greenhaff
P L
PL
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002976:Clenbuterol / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D006984:Hypertrophy; D007536:Isomerism; D008297:Male; D018656:Muscle Fibers, Fast-Twitch / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D018657:Muscle Fibers, Slow-Twitch / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D009929:Organ Size; D051381:Rats; D011916:Rats, Inbred F344
D000318:Adrenergic beta-Agonists; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D018995:Myosin Heavy Chains; D002976:Clenbuterol