Hundal H S, Babij P, Taylor P M, Watt P W, Rennie M J
Department of Anatomy & Physiology, The University, Dundee, U.K.
Biochim Biophys Acta. 1991 May 17;1092(3):376-83. doi: 10.1016/s0167-4889(97)90015-x.
Intramuscular glutamine falls with injury and disease in circumstances associated with increases in blood corticosteroids. We have investigated the effects of corticosteroid administration (0.44 mg/kg dexamethasone daily for 8 days, 200 g female rats) on intramuscular glutamine and Na+, muscle glutamine metabolism and sarcolemmal glutamine transport in the perfused hindlimb. After dexamethasone treatment intramuscular glutamine fell by 45% and Na+ rose by 25% (the respective muscle/plasma distribution ratios changed from 8.6 to 4.5 and 0.12 to 0.15); glutamine synthetase and glutaminase activities were unchanged at 475 +/- 75 and 60 +/- 19 nmol/g muscle per min. Glutamine output by the hindlimb of anaesthetized rats was increased from 31 to 85 nmol/g per min. Sarcolemmal glutamine transport was studied by paired-tracer dilution in the perfused hindlimb: the maximal capacity (Vmax) for glutamine transport into muscle (by Na(+)-glutamine symport) fell from 1058 +/- 310 to 395 +/- 110 nmol/g muscle per min after dexamethasone treatment, accompanied by a decrease in the Km (from 8.1 +/- 1.9 to 2.1 +/- 0.4 mM glutamine). At physiological plasma glutamine concentration (0.75 mM) dexamethasone appeared to cause a proportional increase in sarcolemmal glutamine efflux over influx. Addition of dexamethasone (200 nM) to the perfusate of control rat hindlimbs caused acute changes in Vmax and Km of glutamine transport similar to those resulting from 8-day dexamethasone treatment. The reduction in muscle glutamine concentration after dexamethasone treatment may be primarily due to a reduction in the driving force for intramuscular glutamine accumulation, i.e., in the Na+ electrochemical gradient. The prolonged increase in muscle glutamine output after dexamethasone treatment (which occurs despite a reduction in the size of the intramuscular glutamine pool) appears to be due to a combination of (a) accelerated sarcolemmal glutamine efflux and (b) increased intramuscular synthesis of glutamine.
在血液皮质类固醇增加的情况下，肌肉内谷氨酰胺会随着损伤和疾病而减少。我们研究了皮质类固醇给药（200克雌性大鼠，每天0.44毫克/千克地塞米松，持续8天）对灌注后肢肌肉内谷氨酰胺和钠离子、肌肉谷氨酰胺代谢以及肌膜谷氨酰胺转运的影响。地塞米松治疗后，肌肉内谷氨酰胺下降了45%，钠离子上升了25%（各自的肌肉/血浆分布比率从8.6变为4.5，从0.12变为0.15）；谷氨酰胺合成酶和谷氨酰胺酶活性在475±75和60±19纳摩尔/克肌肉每分钟时保持不变。麻醉大鼠后肢的谷氨酰胺输出量从31增加到85纳摩尔/克每分钟。通过灌注后肢的成对示踪剂稀释法研究了肌膜谷氨酰胺转运：地塞米松治疗后，谷氨酰胺转运进入肌肉（通过钠离子-谷氨酰胺同向转运）的最大容量（Vmax）从1058±310下降到395±110纳摩尔/克肌肉每分钟，同时米氏常数（Km）降低（从8.1±1.9到2.1±0.4毫摩尔谷氨酰胺）。在生理血浆谷氨酰胺浓度（0.75毫摩尔）下，地塞米松似乎导致肌膜谷氨酰胺流出相对于流入成比例增加。向对照大鼠后肢灌注液中添加地塞米松（200纳摩尔）会引起谷氨酰胺转运的Vmax和Km的急性变化，类似于8天地塞米松治疗后的变化。地塞米松治疗后肌肉谷氨酰胺浓度的降低可能主要是由于肌肉内谷氨酰胺积累的驱动力降低，即钠离子电化学梯度降低。地塞米松治疗后肌肉谷氨酰胺输出的长期增加（尽管肌肉内谷氨酰胺池大小减少仍会发生）似乎是由于（a）肌膜谷氨酰胺流出加速和（b）肌肉内谷氨酰胺合成增加共同作用的结果。
