TY - JOUR
T1 - Beta2-adrenoceptor agonist salbutamol increases protein turnover rates and alters signalling in skeletal muscle after resistance exercise in young men
AU - Hostrup, Morten
AU - Reitelseder, Søren
AU - Jessen, Søren
AU - Kalsen, Anders
AU - Nyberg, Michael Permin
AU - Egelund, Jon
AU - Kreiberg, Michael
AU - Maag Kristensen, Caroline
AU - Thomassen, Martin
AU - Pilegaard, Henriette
AU - Backer, Vibeke
AU - Jacobson, Glenn A
AU - Holm, Lars
AU - Bangsbo, Jens
N1 - CURIS 2018 NEXS 268
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Key points: Animal models have shown that beta2-adrenoceptor stimulation increases protein synthesis and attenuates breakdown processes in skeletal muscle. Thus, the beta2-adrenoceptor is a potential target in the treatment of disuse-, disease- and age-related muscle atrophy. In the present study, we show that a few days of oral treatment with the commonly prescribed beta2-adrenoceptor agonist, salbutamol, increased skeletal muscle protein synthesis and breakdown during the first 5 h after resistance exercise in young men. Salbutamol also counteracted a negative net protein balance in skeletal muscle after resistance exercise. Changes in protein turnover rates induced by salbutamol were associated with protein kinase A-signalling, activation of Akt2 and modulation of mRNA levels of growth-regulating proteins in skeletal muscle. These findings indicate that protein turnover rates can be augmented by beta2-adrenoceptor agonist treatment during recovery from resistance exercise in humans. Abstract: 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, cross-over study investigating 12 trained men, the effects of beta2-agonist (6 × 4 mg oral salbutamol) on protein turnover rates, intracellular signalling and mRNA response in skeletal muscle were investigated 0.5–5 h after quadriceps resistance exercise. Each trial was preceded by a 4-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, intracellular signalling and mRNA response were measured in muscle biopsies. The mean (95% confidence interval) myofibrillar fractional synthesis rate was higher for salbutamol than placebo [0.079 (95% CI, 0.064 to 0.093) vs. 0.066 (95% CI, 0.056 to 0.075%) × h−1] (P < 0.05). Mean net leg phenylalanine balance 0.5–5 h after exercise was higher for salbutamol than placebo [3.6 (95% CI, 1.0 to 6.2 nmol) × min−1 × 100 gLeg Lean Mass −1] (P < 0.01). Phosphorylation of Akt2, cAMP response element binding protein 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, Forkhead box protein O1, myostatin and Smad3 mRNA content was higher (P < 0.01) for salbutamol than placebo 0.5 h after exercise, as well as Forkhead box protein O1 and myostatin mRNA content 5 h after exercise, whereas ActivinRIIB mRNA content was lower (P < 0.01) for salbutamol 5 h after exercise. 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, as well as modulation of mRNA response of growth-regulating proteins.
AB - Key points: Animal models have shown that beta2-adrenoceptor stimulation increases protein synthesis and attenuates breakdown processes in skeletal muscle. Thus, the beta2-adrenoceptor is a potential target in the treatment of disuse-, disease- and age-related muscle atrophy. In the present study, we show that a few days of oral treatment with the commonly prescribed beta2-adrenoceptor agonist, salbutamol, increased skeletal muscle protein synthesis and breakdown during the first 5 h after resistance exercise in young men. Salbutamol also counteracted a negative net protein balance in skeletal muscle after resistance exercise. Changes in protein turnover rates induced by salbutamol were associated with protein kinase A-signalling, activation of Akt2 and modulation of mRNA levels of growth-regulating proteins in skeletal muscle. These findings indicate that protein turnover rates can be augmented by beta2-adrenoceptor agonist treatment during recovery from resistance exercise in humans. Abstract: 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, cross-over study investigating 12 trained men, the effects of beta2-agonist (6 × 4 mg oral salbutamol) on protein turnover rates, intracellular signalling and mRNA response in skeletal muscle were investigated 0.5–5 h after quadriceps resistance exercise. Each trial was preceded by a 4-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, intracellular signalling and mRNA response were measured in muscle biopsies. The mean (95% confidence interval) myofibrillar fractional synthesis rate was higher for salbutamol than placebo [0.079 (95% CI, 0.064 to 0.093) vs. 0.066 (95% CI, 0.056 to 0.075%) × h−1] (P < 0.05). Mean net leg phenylalanine balance 0.5–5 h after exercise was higher for salbutamol than placebo [3.6 (95% CI, 1.0 to 6.2 nmol) × min−1 × 100 gLeg Lean Mass −1] (P < 0.01). Phosphorylation of Akt2, cAMP response element binding protein 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, Forkhead box protein O1, myostatin and Smad3 mRNA content was higher (P < 0.01) for salbutamol than placebo 0.5 h after exercise, as well as Forkhead box protein O1 and myostatin mRNA content 5 h after exercise, whereas ActivinRIIB mRNA content was lower (P < 0.01) for salbutamol 5 h after exercise. 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, as well as modulation of mRNA response of growth-regulating proteins.
KW - Adrenergic
KW - Adrenoceptor
KW - Albuterol
KW - Beta-agonists
KW - Doping
KW - Hypertrophy
KW - LABA
KW - Metabolism
KW - SABA
KW - Strength
KW - Training
U2 - 10.1113/jp275560
DO - 10.1113/jp275560
M3 - Journal article
C2 - 29968301
AN - SCOPUS:85051025375
SN - 0022-3751
VL - 596
SP - 4121
EP - 4139
JO - The Journal of Physiology
JF - The Journal of Physiology
IS - 17
ER -