Exercise Biology, Department of Public Health, Aarhus University, Aarhus, Denmark.
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
J Physiol. 2024 Jun;602(12):2807-2822. doi: 10.1113/JP285995. Epub 2024 May 19.
Piperine has been shown to bind to myosin and shift the distribution of conformational states of myosin molecules from the super-relaxed state to the disordered relaxed state. However, little is known about the implications for muscle force production and potential underlying mechanisms. Muscle contractility experiments were performed using isolated muscles and single fibres from rats and mice. The dose-response effect of piperine on muscle force was assessed at several stimulation frequencies. The potentiation of muscle force was also tested in muscles fatigued by eccentric contractions. Potential mechanisms of force potentiation were assessed by measuring Ca levels during stimulation in enzymatically dissociated muscle fibres, while myofibrillar Ca sensitivity was assessed in chemically skinned muscle fibres. Piperine caused a dose-dependent increase in low-frequency force with no effect on high-frequency force in both slow- and fast-twitch muscle, with similar relative increases in twitch force, rate of force development and relaxation rate. The potentiating effect of piperine on low-frequency force was reversible, and piperine partially recovered low-frequency force in fatigued muscle. Piperine had no effect on myoplasmic free [Ca] levels in mouse muscle fibres, whereas piperine substantially augmented the force response to submaximal levels of [Ca] in rat MyHCII fibres and MyHCI fibres along with a minor increase in maximum Ca-activated force. Piperine enhances low-frequency force production in both fast- and slow-twitch muscle. The effects are reversible and can counteract muscle fatigue. The primary underlying mechanism appears to be an increase in Ca sensitivity. KEY POINTS: Piperine is a plant alkaloid derived from black pepper. It is known to bind to skeletal muscle myosin and enhance resting ATP turnover but its effects on contractility are not well known. We showed for the first time a piperine-induced force potentiation that was pronounced during low-frequency electrical stimulation of isolated muscles. The effect of piperine was observed in both slow and fast muscle types, was reversible, and could counteract the force decrements observed after fatiguing muscle contractions. Piperine treatment caused an increase in myofibrillar Ca sensitivity in chemically skinned muscle fibres, while we observed no effect on intracellular Ca concentrations during electrical stimulation in enzymatically dissociated muscle fibres.
胡椒碱已被证明可与肌球蛋白结合，并将肌球蛋白分子构象状态的分布从超松弛状态转移到无序松弛状态。然而，对于肌肉力量产生的影响和潜在的潜在机制知之甚少。使用来自大鼠和小鼠的分离肌肉和单个纤维进行肌肉收缩实验。在几种刺激频率下评估胡椒碱对肌肉力量的剂量反应效应。还在经过偏心收缩疲劳的肌肉中测试了肌肉力量的增强作用。通过测量酶解分离的肌肉纤维在刺激过程中的 Ca 水平来评估力增强的潜在机制，同时在化学剥皮的肌肉纤维中评估肌球蛋白 Ca 敏感性。胡椒碱在慢肌和快肌中均引起低频力的剂量依赖性增加，而对高频力无影响，在 twitch 力、力发展速率和松弛速率方面具有相似的相对增加。胡椒碱对低频力的增强作用是可逆的，并且胡椒碱可部分恢复疲劳肌肉中的低频力。胡椒碱对小鼠肌肉纤维中的细胞质游离 [Ca]水平没有影响，而胡椒碱可大大增强大鼠 MyHCII 纤维和 MyHCI 纤维对亚最大水平 [Ca]的力反应，同时最大 Ca 激活力略有增加。胡椒碱增强快肌和慢肌的低频力产生。这些作用是可逆的，可以抵抗肌肉疲劳。主要潜在机制似乎是 Ca 敏感性增加。关键点：胡椒碱是一种源自黑胡椒的植物生物碱。已知它可与骨骼肌肌球蛋白结合并增强静止 ATP 周转率，但对其收缩性的影响尚不清楚。我们首次显示出胡椒碱诱导的力增强作用，在分离肌肉的低频电刺激下表现明显。该作用在慢肌和快肌两种类型中均观察到，是可逆的，并且可以抵消疲劳肌肉收缩后观察到的力下降。胡椒碱处理导致化学剥皮的肌肉纤维中肌球蛋白 Ca 敏感性增加，而在酶解分离的肌肉纤维中电刺激期间观察到细胞内 Ca 浓度没有影响。
