Beta2-adrenoceptor agonist salbutamol increases protein turnover rates and alters signalling in skeletal muscle after resistance exercise in young men
Hostrup, M and Reitelseder, S and Jessen, S and Kalsen, A and Nyberg, M and Egelund, J and Kreiberg, M and Kristensen, CM and Thomassen, M and Pilegaard, H and Backer, V and Jacobson, GA and Holm, L and Bangsbo, J, Beta2-adrenoceptor agonist salbutamol increases protein turnover rates and alters signalling in skeletal muscle after resistance exercise in young men, Journal of Physiology, 596, (17) pp. 4121-4139. ISSN 0022-3751 (2018) [Refereed Article]
The effect of beta2-adrenoceptor stimulation on skeletal muscle protein turnover and intracellular signalling is insufficiently explored in humans, particularly in association with exercise. In a randomized placebo-controlled crossover study with 12 trained men, the effect of beta2-agonist (6×4 mg oral salbutamol) on protein turnover rates, intracellular signalling, and mRNA response in skeletal muscle was investigated 0.5-5 h after quadriceps resistance exercise. Each trial was preceded by a four-day lead-in treatment period. Leg protein turnover rates were assessed by infusion of [13C6]-phenylalanine and sampling of arterial and venous blood as well as vastus lateralis muscle biopsies 0.5 and 5 h after exercise. Furthermore, myofibrillar fractional synthesis rate (FSR), intracellular signalling and mRNA response were measured in muscle biopsies. Mean (±95%CI) myofibrillar FSR was higher for salbutamol than placebo [0.079(±0.007) vs. 0.066(±0.004) × h-1](p<0.05). Mean net leg phenylalanine balance 0.5-5 h after exercise was [3.6(±2.6) nmol×min-1 × 100 gLeg Lean Mass-1] higher for salbutamol than placebo (p<0.01). Phosphorylation of Akt2, CREB and PKA-substrate 0.5 and 5 h after exercise as well as phosphorylation of eEF2 5 h after exercise was higher (p<0.05) for salbutamol than placebo. Calpain-1, FoxO1, myostatin and Smad3 mRNA content was higher (p<0.01) for salbutamol than placebo 0.5 h after exercise, and FoxO1 and myostatin mRNA content 5 h after, whereas ActivinRIIB mRNA content was lower (p<0.01) for salbutamol 5 h after. These observations suggest that beta2-agonist increases protein turnover rates in skeletal muscle after resistance exercise in humans, with concomitant cAMP/PKA and Akt2 signalling, and modulation of mRNA response of growth-regulating proteins.