Effects of tadalafil on skeletal muscle tissue: exploring interactions and novel mechanisms of action.

IF 2.5 Q3 ENDOCRINOLOGY & METABOLISM Minerva endocrinology Pub Date : 2023-06-01 DOI:10.23736/S2724-6507.21.03698-8
Cristina Antinozzi, Emanuela A Greco, Paolo Sgrò, Ivan Dimauro, Antonio Aversa, Luigi DI Luigi
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引用次数: 2

Abstract

Beside its mechanical roles in controlling posture and locomotion, skeletal muscle system, the largest insulin and steroid hormones target tissue, plays a key role in influencing thermoregulation, secondary sexual characteristics, hormones metabolism, and glucose uptake and storage, as well as energetic metabolism. Indeed, in addition to insulin, several hormones influence the skeletal muscle metabolism/function and/or are influenced by skeletal muscles activity (i.e., physical exercise). Particularly, steroid hormones play a key role in modulating many biological processes in muscles, essential for overall muscle's function and homeostasis, both at rest and during all physical activities (i.e., physical exercise, muscular work). Phosphodiesterase type 5 (PDE5) is the enzyme engaged to hydrolyze cyclic guanosine monophosphate (cGMP) in inactive 5'-GMP form. Therefore, through the inhibition of this enzyme, the intracellular level of cGMP increases, and the cGMP-related cellular responses are prolonged. Different drugs inhibiting PDE5 (PDE5i) exist, and the commercially available PDE5i are sildenafil, vardenafil, tadalafil, and avanafil. The PDE5i tadalafil may influence cellular physiology and endocrine-metabolic pathways in skeletal muscles and exerts its functions both by activating the cell signaling linked to the insulin-related metabolic pathways and modulating the endocrine responses, protein catabolism and hormone-related anabolism/catabolism during and after physical exercise-related stress. Based on recent in-vivo and in-vitro findings, in this narrative review the aim was to summarize the available evidence describing the interactions between the PDE5i tadalafil and steroid hormones in skeletal muscle tissue and physical exercise adaptation, focusing our interest on their possible synergistic or competitive action(s) on muscle metabolism and function.

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他达拉非对骨骼肌组织的影响:探索相互作用和新的作用机制。
骨骼肌系统作为胰岛素和类固醇激素的最大靶组织,除了在控制姿态和运动方面的机械作用外,还在影响体温调节、第二性征、激素代谢、葡萄糖摄取和储存以及能量代谢等方面发挥关键作用。事实上,除胰岛素外,还有几种激素影响骨骼肌代谢/功能和/或受骨骼肌活动(即体育锻炼)的影响。特别是,类固醇激素在调节肌肉中的许多生物过程中起着关键作用,对肌肉的整体功能和体内平衡至关重要,无论是在休息时还是在所有体育活动(即体育锻炼,肌肉工作)中。磷酸二酯酶5 (PDE5)是一种酶,用于水解无活性的5'-GMP形式的环鸟苷单磷酸(cGMP)。因此,通过抑制该酶,细胞内cGMP水平升高,cGMP相关的细胞反应延长。抑制PDE5 (PDE5i)的药物不同,市售的PDE5i有西地那非、伐地那非、他达拉非和阿那非。PDE5i他达拉非可能影响骨骼肌的细胞生理和内分泌代谢途径,通过激活与胰岛素相关的代谢途径相关的细胞信号,调节运动相关应激期间和应激后的内分泌反应、蛋白质分解代谢和激素相关的合成代谢/分解代谢来发挥作用。基于最近在体内和体外的研究结果,本文的目的是总结现有的证据,描述PDE5i他达拉非和骨骼肌组织中的类固醇激素和体育锻炼适应之间的相互作用,重点关注它们在肌肉代谢和功能上可能的协同或竞争作用。
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CiteScore
4.60
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0.00%
发文量
146
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