Chesney R W, Jolly K, Zelikovic I, Iwahashi C, Lohstroh P
Department of Pediatrics, University of California-Davis 95616.
FASEB J. 1989 Jul;3(9):2081-5. doi: 10.1096/fasebj.3.9.2744305.
The renal adaptive response to a varied intake of sulfur amino acids is demonstrated by an increase in the initial rate of Na+-taurine symport (cotransport) by rat renal brush border membrane vesicles (BBMVs) after 8-14 days of a low methionine diet. A high (3%) taurine diet reduces Na+-taurine symport. Fasting for 3 days, which depletes renal tubule cell taurine content, also enhances Na+-taurine symport both initially (15 s) and throughout the overshoot. In this study we examine the possibility that a rapid-onset adaptive response is expressed in BBMV, with the increased Na+-taurine symport reflecting the incorporation of preformed symporter into membranes rather than new synthesis. Rats fed the low methionine diet for 14 days were placed on the high taurine diet for 12-18 h; Na+-taurine symport activity fell by 40%. Fasting for 4 h restored low methionine diet levels of Na+-taurine symport activity (92 pmol.mg protein-1.15 s-1), defining a rapidly induced rise in uptake. Colchicine (0.6 mg) was injected prior to fasting in a group of rats because it blocks the incorporation (import) of preformed symporter into the membrane. Animals injected with colchicine had a pattern of BBMV uptake similar to that found in animals switched to the high taurine diet for 18 h. This agent blocked the rapidly induced rise in uptake. Feeding with the high taurine diet for 4 h caused a fall in uptake of 16.5%; colchicine blocked this reduction in uptake. These results indicate that the nephron can respond rapidly to changes in the intake of amino acids, conserving taurine in periods of nutrient lack and excreting excess taurine within 4 h in periods of surfeit. This rapid response is expressed at the brush border surface. The use of cholchicine indicates that the increase or reduction in Na+-taurine symport activity is due to incorporation (import) of transporter into the BBMV rather than to de novo synthesis.
低蛋氨酸饮食8 - 14天后，大鼠肾刷状缘膜囊泡（BBMVs）对Na⁺-牛磺酸同向转运（共转运）初始速率的增加，证明了肾脏对不同硫氨基酸摄入量的适应性反应。高（3%）牛磺酸饮食会降低Na⁺-牛磺酸同向转运。禁食3天会耗尽肾小管细胞牛磺酸含量，这也会在初始阶段（15秒）以及整个超调期增强Na⁺-牛磺酸同向转运。在本研究中，我们探讨了BBMV中是否表达了快速起效的适应性反应，Na⁺-牛磺酸同向转运增加反映了预先形成的同向转运体并入膜中而非新合成。给喂食低蛋氨酸饮食14天的大鼠喂食高牛磺酸饮食12 - 18小时；Na⁺-牛磺酸同向转运活性下降了40%。禁食4小时可恢复低蛋氨酸饮食水平的Na⁺-牛磺酸同向转运活性（92 pmol·mg蛋白⁻¹·15 s⁻¹），这确定了摄取量的快速诱导增加。在一组大鼠禁食前注射秋水仙碱（0.6毫克），因为它会阻断预先形成的同向转运体并入膜中。注射秋水仙碱的动物的BBMV摄取模式与切换到高牛磺酸饮食18小时的动物相似。这种药物阻断了摄取量的快速诱导增加。喂食高牛磺酸饮食4小时导致摄取量下降16.5%；秋水仙碱阻断了这种摄取量的减少。这些结果表明，肾单位可以对氨基酸摄入量的变化迅速做出反应，在营养缺乏时期保留牛磺酸，并在过量时期4小时内排出多余的牛磺酸。这种快速反应在刷状缘表面表达。秋水仙碱的使用表明，Na⁺-牛磺酸同向转运活性的增加或降低是由于转运体并入BBMV中，而不是从头合成。
