Gómez-Amores Lucía, Mate Alfonso, Vázquez Carmen M
Department of Physiology and Zoology, Faculty of Pharmacy, University of Seville, E-41012 Seville, Spain.
Pharm Res. 2003 Aug;20(8):1133-40. doi: 10.1023/a:1025080426970.
To examine the effect of long-term administration of L-carnitine on L-carnitine transport in renal brush-border membrane vesicles (BBMVs) from normotensive, Wistar-Kyoto rats.
Rats (n = 20) were orally administered 0.2 g carnitine/kg body weight per day for a total period of 8 weeks. Kinetic parameters of L-carnitine uptake were calculated by non-linear regression, and the relative abundance of the carnitine transporter, OCTN2, was determined by Western blot analysis.
Initial rates and maximal overshoot levels of Na+-dependent L-carnitine transport were significantly reduced in BBMVs from L-carnitine-treated rats compared with untreated animals. Similarly, the maximal transport rate (Vmax) of OCTN2 was lower in treated rats. However, no differences were observed in the Michaelis constant (Km) or the diffusion constant (Kd) between the two groups of animals. The amount of OCTN2 protein was also decreased in L-carnitine-fed rats, this reduction being similar to that of the Vmax. These results were accompanied by an increase in the serum levels and also in the renal excretion of both free and esterified carnitine in treated rats, indicating that the long-term administration of L-carnitine leads to increased renal carnitine clearance.
These findings suggest a downregulation of OCTN2 at the renal level, in the presence of high levels of carnitine.
研究长期给予L-肉碱对正常血压的Wistar-Kyoto大鼠肾刷状缘膜囊泡（BBMVs）中L-肉碱转运的影响。
20只大鼠每天口服0.2 g/kg体重的肉碱，共8周。通过非线性回归计算L-肉碱摄取的动力学参数，并通过蛋白质免疫印迹分析确定肉碱转运体OCTN2的相对丰度。
与未处理的动物相比，L-肉碱处理的大鼠的BBMVs中，Na+依赖性L-肉碱转运的初始速率和最大超调水平显著降低。同样，处理组大鼠中OCTN2的最大转运速率（Vmax）较低。然而，两组动物之间的米氏常数（Km）或扩散常数（Kd）没有差异。L-肉碱喂养的大鼠中OCTN2蛋白的量也减少，这种减少与Vmax的减少相似。这些结果伴随着处理组大鼠血清水平以及游离和酯化肉碱的肾排泄增加，表明长期给予L-肉碱导致肾肉碱清除率增加。
这些发现表明，在肉碱水平较高的情况下，肾水平的OCTN2会下调。
