Section of Integrative Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.
Department of Respiratory Medicine, Bispebjerg University Hospital, Copenhagen, Denmark.
J Physiol. 2018 Sep;596(17):4121-4139. doi: 10.1113/JP275560. Epub 2018 Jul 30.
Animal models have shown that beta -adrenoceptor stimulation increases protein synthesis and attenuates breakdown processes in skeletal muscle. Thus, the beta -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 beta -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 beta -adrenoceptor agonist treatment during recovery from resistance exercise in humans.
The effect of beta -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 beta -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 [ C ]-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 ] (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 × 100 g ] (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 beta -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.
动物模型表明，β-肾上腺素受体刺激可增加骨骼肌中的蛋白质合成并减弱分解过程。因此，β-肾上腺素受体是治疗废用性、疾病和与年龄相关的肌肉萎缩的潜在靶点。在本研究中，我们表明，口服给予常用的β-肾上腺素受体激动剂沙丁胺醇数天，可增加年轻男性抗阻运动后 5 小时内的骨骼肌蛋白质合成和分解。沙丁胺醇还可抵抗抗阻运动后骨骼肌的净蛋白负平衡。沙丁胺醇诱导的蛋白质周转率变化与蛋白激酶 A 信号转导、Akt2 的激活以及骨骼肌生长调节蛋白的 mRNA 水平的调节有关。这些发现表明，β-肾上腺素受体激动剂治疗可在人类抗阻运动后的恢复过程中增强蛋白质周转率。
β-肾上腺素受体刺激对人类骨骼肌蛋白质周转率和细胞内信号转导的影响尚未得到充分研究，特别是与运动有关。在一项随机、安慰剂对照、交叉研究中，调查了 12 名训练有素的男性，在股四头肌抗阻运动后 0.5-5 小时，β-激动剂（6×4mg 口服沙丁胺醇）对骨骼肌蛋白质周转率、细胞内信号转导和 mRNA 反应的影响。每个试验都有一个为期 4 天的先导治疗期。通过[C]苯丙氨酸输注和动脉及静脉血取样以及股外侧肌活检，在运动后 0.5 和 5 小时评估腿部蛋白质周转率。此外，还测量了肌原纤维的合成率、细胞内信号转导和肌肉活检的 mRNA 反应。与安慰剂相比，沙丁胺醇的肌原纤维合成率更高[0.079（95%置信区间，0.064 至 0.093）比 0.066（95%置信区间，0.056 至 0.075）×h]（P<0.05）。与安慰剂相比，运动后 0.5-5 小时的腿部苯丙氨酸净平衡更高[3.6（95%置信区间，1.0 至 6.2 nmol）×min×100 g]（P<0.01）。与安慰剂相比，运动后 0.5 和 5 小时的 Akt2、cAMP 反应元件结合蛋白和 PKA 底物磷酸化以及运动后 5 小时的 eEF2 磷酸化更高（P<0.05）。与安慰剂相比，运动后 0.5 小时的钙蛋白酶 1、叉头框蛋白 O1、肌肉生长抑制素和 Smad3 mRNA 含量更高（P<0.01），运动后 5 小时的叉头框蛋白 O1 和肌肉生长抑制素 mRNA 含量更高，而运动后 5 小时的激活素受体 IIB mRNA 含量更低（P<0.01）。这些观察结果表明，β-激动剂可增加人类抗阻运动后骨骼肌中的蛋白质周转率，同时伴有 cAMP/PKA 和 Akt2 信号转导以及生长调节蛋白的 mRNA 反应调节。
