Beta-agonist-induced alterations in organ weights and protein content: comparison of racemic clenbuterol and its enantiomers.
Beta-agonist-induced alterations in organ weights and protein content: comparison of racemic clenbuterol and its enantiomers.
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DOI：
10.1002/1520-636x(2000)12:8
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发表时间：
2000
期刊：
影响因子：
2
通讯作者：
D. Deutsch;Imad K. Abukhalaf;L. Wineski;Hassan Y. Aboul-Enein;Sidney A. Pitts;Brian A. Parks;Robert A. Oster;Douglas F. Paulsen;David E. Potter
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文献类型：
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作者：
D. Deutsch;Imad K. Abukhalaf;L. Wineski;Hassan Y. Aboul-Enein;Sidney A. Pitts;Brian A. Parks;Robert A. Oster;Douglas F. Paulsen;David E. Potter
克伦特罗是一种选择性较高的β2-肾上腺素能部分激动剂，具有支气管扩张活性。这种药物已经被研究为一种潜在的对策，用于治疗因推测的合成代谢作用而导致的微重力或停用引起的骨骼肌萎缩。本研究的目的是：1)分析克伦特罗(-)-R和(+)-S对映体(0.2 mg/kg)对肌肉和骨骼肌等器官的合成代谢作用；2)比较对映体对消旋体(0.4 mg/kg和1.0 mg/kg)的反应。雄性SD大鼠给予：a)外消旋克伦特罗(RAC-Clenbuterol，0.4或1.0 mg/kg)，b)对映体[Clenbuterol(-)-R或(+)-S]，c)赋形剂(1.0mL/kg缓冲生理盐水)。通过测量组织质量和蛋白质含量来确定合成代谢活性。采用高效液相色谱手性固定相直接拆分克伦特罗对映体。在骨骼肌中，这两种对映体具有相同的合成代谢活性，其影响是肌肉和解剖区域特有的。尽管对映体不影响心脏重量与体重的比率，但克伦特罗(+)-S可引起小而显著的心脏重量增加。这两种克伦特罗对映体都显著增加了骨骼肌质量，但与外消旋混合物相比，在产生心肌肥大方面活性较低。
Clenbuterol is a relatively selective beta2-adrenergic partial agonist that has bronchodilator activity. This drug has been investigated as a potential countermeasure to microgravity- or disuse-induced skeletal muscle atrophy because of presumed anabolic effects. The purpose of this study was to: 1) analyze the anabolic effect of clenbuterol's (-)-R and (+)-S enantiomers (0.2 mg/kg) on muscles (cardiac and skeletal) and other organs; and 2) compare responses of enantiomers to the racemate (0.4 mg/kg and 1.0 mg/kg). Male Sprague Dawley rats were treated with: a) racemic clenbuterol (rac-clenbuterol, 0.4 or 1.0 mg/kg); b) enantiomers [clenbuterol (-)-R or (+)-S]; or c) vehicle (1.0 mL/kg buffered saline). Anabolic activity was determined by measuring tissue mass and protein content. HPLC teicoplanin chiral stationary phase was used to directly resolve racemic clenbuterol to its individual enantiomers. In skeletal muscle, both enantiomers had equal anabolic activity, and the effects were muscle- and anatomic region-specific in magnitude. Although the enantiomers did not affect the ventricular mass to body weight ratio, clenbuterol (+)-S induced a small but significant increase in ventricular mass. Both clenbuterol enantiomers produced significant increases in skeletal muscle mass, while being less active in producing cardiac ventricular muscle hypertrophy than the racemic mixture.