Beta2-adrenoceptor agonist salbutamol increases protein turnover rates and alters signalling in skeletal muscle after resistance exercise in young men

Morten Hostrup; Søren Reitelseder; Søren Jessen; Anders Kalsen; Michael Permin Nyberg; Jon Egelund; Michael Kreiberg; Caroline Maag Kristensen; Martin Thomassen; Henriette Pilegaard; Vibeke Backer; Glenn A Jacobson; Lars Holm; Jens Bangsbo

doi:10.1113/jp275560

Beta₂-adrenoceptor agonist salbutamol increases protein turnover rates and alters signalling in skeletal muscle after resistance exercise in young men

Morten Hostrup^*, Søren Reitelseder, Søren Jessen, Anders Kalsen, Michael Permin Nyberg, Jon Egelund, Michael Kreiberg, Caroline Maag Kristensen, Martin Thomassen, Henriette Pilegaard, Vibeke Backer, Glenn A Jacobson, Lars Holm, Jens Bangsbo

^*Corresponding author for this work

18 Citations (Scopus)

Abstract

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 g_{Leg 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.

Original language	English
Journal	Journal of Physiology
Volume	596
Issue number	17
Pages (from-to)	4121-4139
Number of pages	19
ISSN	0022-3751
DOIs	https://doi.org/10.1113/jp275560
Publication status	Published - 1 Sept 2018

Keywords

Adrenergic
Adrenoceptor
Albuterol
Beta-agonists
Doping
Hypertrophy
LABA
Metabolism
SABA
Strength
Training

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Hostrup, M., Reitelseder, S., Jessen, S., Kalsen, A., Nyberg, M. P., Egelund, J., Kreiberg, M., Maag Kristensen, C., Thomassen, M., Pilegaard, H., Backer, V., Jacobson, G. A., Holm, L., & Bangsbo, J. (2018). 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), 4121-4139. https://doi.org/10.1113/jp275560

Beta₂-adrenoceptor agonist salbutamol increases protein turnover rates and alters signalling in skeletal muscle after resistance exercise in young men. / Hostrup, Morten; Reitelseder, Søren; Jessen, Søren et al.
In: Journal of Physiology, Vol. 596, No. 17, 01.09.2018, p. 4121-4139.

Research output: Contribution to journal › Journal article › Research › peer-review

Hostrup, M, Reitelseder, S, Jessen, S, Kalsen, A, Nyberg, MP, Egelund, J, Kreiberg, M, Maag Kristensen, C, Thomassen, M , Pilegaard, H , Backer, V, Jacobson, GA, Holm, L & Bangsbo, J 2018, 'Beta₂-adrenoceptor agonist salbutamol increases protein turnover rates and alters signalling in skeletal muscle after resistance exercise in young men', Journal of Physiology, vol. 596, no. 17, pp. 4121-4139. https://doi.org/10.1113/jp275560

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abstract = "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.",

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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

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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 - Journal of Physiology

JF - Journal of Physiology

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