Cooper G J, Kohn P G
J Physiol. 1980 May;302:89-105. doi: 10.1113/jphysiol.1980.sp013231.
The non-metabolizable amino acid alpha-aminoisobutyric acid (AIB) has been used to study the effects of insulin and a number of membrane stabilizers on amino acid transport in rat soleus muscle in an attempt to characterize the mechanisms present. 2. Insulin (5--100 millimicron./ml) increases the net uptake of AIB two- to threefold. Since insulin is without significant effects on AIB efflux, stimulation of net uptake appears to result directly from an increased AIB influx. 3. All classes of membrane stabilizer tested affected AIB fluxes but the responses observed varied for different classes of compounds. 4. The total anaesthetic, tetracaine, reduced AIB accumulation both in the absence and presence of insulin by a similar proportion. The effects on AIB efflux were dependent on the concentration of tetracaine used. Efflux was suppressed by concentrations up to 1 mM whereas 4 mM-tetracaine caused a massive stimulation of AIB efflux. Other local anaesthetics and barbiturates produced similar effects. 5. Another group of membrane stabilizers, exemplified by chlorpromazine, also suppressed AIB uptake, but at no concentration did they reduce AIB efflux. In fact, efflux of AIB began to be increased at concentrations of chlorpromazine which were giving only a modest inhibition of uptake. 6. Measurement of the initial rate of uptake showed that it involved two components. Tetracaine appears to inhibit the saturable component whilst leaving the non-saturable component relatively unaffected. 7. The active uptake of AIB was shown to be Na+-dependent, and under Na+-free conditions tetracaine had no effect on the initial rate of uptake. The non-saturable component was also shown to be Na+-sensitive, uptake from high extracellular concentrations of AIB being reduced in Na+-free media. 8. The possibility of the presence of a carrier-mediated AIB efflux mechanism was investigated. AIB efflux was stimulated by extracellular AIB (homo-exchange) or glycine (hetero-exchange), but not mannitol. This suggests the involvement of a carrier-mediated process in AIB efflux. 9. The present study has demonstrated a heterogeneity among different classes of membrane stabilizers in their actions on AIB efflux which is in marked contrast to previous observations of sugar and cation transport in this preparation. Possible reasons for these differences are discussed.
不可代谢的氨基酸α-氨基异丁酸（AIB）已被用于研究胰岛素和多种膜稳定剂对大鼠比目鱼肌氨基酸转运的影响，以试图阐明其中存在的机制。2. 胰岛素（5 - 100微摩尔/毫升）使AIB的净摄取增加两到三倍。由于胰岛素对AIB的外流没有显著影响，因此净摄取的增加似乎直接源于AIB内流的增加。3. 所测试的所有类型的膜稳定剂都影响AIB的通量，但不同类型的化合物观察到的反应有所不同。4. 全身麻醉剂丁卡因在有无胰岛素的情况下均以相似的比例降低AIB的蓄积。对AIB外流的影响取决于所用丁卡因的浓度。浓度高达1毫摩尔时外流受到抑制，而4毫摩尔的丁卡因则引起AIB外流的大量刺激。其他局部麻醉剂和巴比妥类药物也产生类似的效果。5. 另一组以氯丙嗪为代表的膜稳定剂也抑制AIB的摄取，但在任何浓度下都不会降低AIB的外流。事实上，在氯丙嗪浓度仅适度抑制摄取时，AIB的外流就开始增加。6. 对摄取初始速率的测量表明它涉及两个成分。丁卡因似乎抑制可饱和成分，而相对不影响不饱和成分。7. AIB的主动摄取被证明是依赖Na + 的，在无Na + 的条件下丁卡因对摄取初始速率没有影响。不饱和成分也被证明对Na + 敏感，在无Na + 的培养基中，从高细胞外浓度的AIB摄取减少。8. 研究了存在载体介导的AIB外流机制的可能性。细胞外AIB（同型交换）或甘氨酸（异型交换）刺激AIB外流，但甘露醇无此作用。这表明载体介导的过程参与了AIB外流。9. 本研究表明不同类型的膜稳定剂对AIB外流的作用存在异质性，这与此前对该制剂中糖和阳离子转运的观察结果形成显著对比。讨论了这些差异的可能原因。
