Glucocorticoids (GC) are steroid hormones released from the adrenal gland in response to physical and emotional stress. GCs have high anti-inflammatory (glucocorticoid) and insignificant water retention (mineralocorticoid) properties. Therefore, they are widely used in the management of diverse pathological conditions including asthma, rheumatoid arthritis, ulcerative colitis and bacterial meningitis. However, their use is limited because of several side effects including a myopathy, the cause of which is still poorly understood (Stahn and Buttgeriet, 2008). Like other steroid hormones, GCs have both genomic (chronic) and non-genomic (acute) actions. Although the chronic effects of GCs in skeletal muscle have been the subject of numerous previous studies (Schakman et at., 2008), little is known about their acute effects. The primary aim of this study was to investigate the acute effects of beclomethasone, a synthetic GC, in isolated intact mouse fast and slow twitch skeletal muscle fibre bundles. The experiments were performed at 20°C on small skeletal muscle fibre bundles isolated from the extensor digitorum longus (a fast-twitch muscle) and soleus (a slow-twitch muscle) of adult mice. The mice were killed as recommended by the Animals (Scientific Procedures) Act 1986, UK and the experiments conformed to the local animal welfare committee guidelines. Force was measured in the presence and absence of various concentrations of beclomethasone (125, 250 and 500nM) as previously described in Hamdi and Mutungi (2010). In some experiments, the glucocorticoid receptor (GCR) inhibitor mifepristone was added and the expression of the GCR in the fibre bundles was determined. Treatment of the fibre bundles with beclomethasone increased maximum isometric tension (Po) in the slow twitch fibre bundles without significantly affecting that of the fast twitch ones. The increase was maximal at 250nM beclomethasone and was completely abolished by pre-treating the fibre bundles with 10µM mifeprestone. Thus, 250nM beclomethasone led to a 16.3±0.08% (n= 5 fibres, S.E.M) increase in Po) in the slow twitch fibres but only to a 0.8±0.1% (n=5 fibres) increase in the fast-twitch fibres. Examination of GCR expression showed that both fibre types expressed the cytosolic form of the receptor and that its concentration was higher in the slow twitch than in the fast twitch fibres. In contrast, the receptor was found in the membrane fraction of the slow twitch fibre bundles only. These findings suggest that the acute effects of GCs are mediated through a membrane GCR and that at low doses beclomethasone, administered soon after stress, may be protective in slow-twitch skeletal muscle fibres.
Physiology 2012 (Edinburgh) (2012) Proc Physiol Soc 27, C77
Oral Communications: The acute effects of beclomethasone on force in mouse skeletal muscle fibres are both dose and fibre type dependent
G. Mutungi1, J. Cormack2
1. Department of Medicine, University of East Anglia, Norwich, United Kingdom. 2. School of Biological Sciences, University of East Anglia, Norwich, Norfolk, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.