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β2-adrenoceptor agonist formoterol promotes slow-to-fast fibre transitions in rat skeletal muscle

J.G. Ryall, D.R. Plant, G.S. Lynch, Physiology, University of Melbourne, Melbourne, Vic, Australia

It is well established that β2-adrenoceptor agonists (β2-agonists), such as clenbuterol and fenoterol, promote a shift in fibre type expression from slow- (type I) to fast- (type II) twitch fibres1. This shift in phenotype can alter muscle contractile function by increasing rates of contraction and relaxation2. New generation β2-agonists, such as formoterol, have more potent muscle anabolic effects than other β2-agonists such as clenbuterol or fenoterol. However, the ability of formoterol to alter muscle phenotype has not been determined. In this study we treated young, adult Fischer 344 rats for four weeks with either formoterol (2 mg/kg/day, i.p.), or an equal volume of saline vehicle. After treatment, rats were anaesthetised with sodium pentobarbitone and the predominantly (85-90%) slow-twitch soleus muscle was excised and frozen immediately in thawing isopentane. Muscle sections (8 μ m thick) were obtained for histological, biochemical and immunohistochemical analyses. Like clenbuterol and fenoterol1, formoterol increased the proportion of the fast type IIa and IId/x fibres in the soleus muscle, with a concomitant decrease in the slow type I fibres, as determined from myosin ATPase histochemistry. Soleus muscles from formoterol treated rats also exhibited a reduced proportion of highly oxidative fibres compared with muscles from untreated control rats. The ability of β2-agonists like formoterol to cause slow- to fast fibre transitions contributes to their ability to alter skeletal muscle contraction.

Supported by the Muscular Dystrophy Association (USA). JGR is supported by the National Heart Foundation (Australia).

(1) Schertzer JD, Ryall JG, Plant DR, Harrap SB, Lynch GS. FASEB Journal. 2004; 18 suppl:A1288.

(2) Ryall JG, Gregorevic P, Plant DR, Sillence MN, Lynch GS. American Journal of Physiology. 2002; 283:1386-1394.