Langen Karl-Josef, Hamacher Kurt, Bauer Dagmar, Bröer Stefan, Pauleit Dirk, Herzog Hans, Floeth Frank, Zilles Karl, Coenen Heinz H
Institute of Medicine, Research Centre Jülich, Jülich, Germany.
J Cereb Blood Flow Metab. 2005 May;25(5):607-16. doi: 10.1038/sj.jcbfm.9600065.
Generally, L-amino acids are preferably transported into mammalian cells compared with their D-isomers, and only L-amino acids are incorporated into proteins. Former studies, however, indicated that D-[H]proline is accumulated in the brain of mice after injection, while L-[3H]proline is not. We investigated the differential cerebral uptake of the D- and L-isomers of the PET tracer cis-4-[18F]fluoroproline (D-/L-cis-FPro) and of D-/L-[3H]proline (D-/L-Pro) in rats by dual tracer autoradiography and the uptake of D-cis-FPro in two human subjects by PET. The standardized uptake value (SUV) of D-cis-FPro in the cerebral cortex of rats 2 h p.i. was 3.05+/-1.18 (n=9) versus 0.06+/-0.01 (n=4) for L-cis-FPro (P<0.001) and 1.29+/-0.27 (n=4) for D-Pro versus 0.30+/-0.14 (n=9) for L-Pro (P<0.001). Analysis of the rat brain tissue after injection of D-cis-FPro (n=3) revealed no radioactivity in the proteins but a relevant part in the form of L-trans-FPro. The PET studies yielded a four- to five-fold higher SUV and influx rate constant in the human cortex for D-cis-FPro than for L-cis-FPro. We conclude that D-cis-FPro and D-Pro are preferably transported at the blood-brain barrier compared with their L-isomers and isomerized to the L-form within the brain. Thus, D-Pro in the plasma might be a source of intracerebral L-proline, which has been shown to act as a modulator of excitatory neurotransmission.
一般来说，与D型异构体相比，L型氨基酸更易被转运进入哺乳动物细胞，并且只有L型氨基酸会被整合到蛋白质中。然而，先前的研究表明，注射后D-[H]脯氨酸会在小鼠脑中积累，而L-[3H]脯氨酸则不会。我们通过双示踪自显影研究了大鼠对PET示踪剂顺式-4-[18F]氟脯氨酸（D-/L-顺式-FPro）和D-/L-[3H]脯氨酸（D-/L-Pro）的D型和L型异构体的脑摄取差异，并通过PET研究了两名人类受试者对D-顺式-FPro的摄取情况。注射后2小时，大鼠大脑皮质中D-顺式-FPro的标准化摄取值（SUV）为3.05±1.18（n = 9），而L-顺式-FPro为0.06±0.01（n = 4）（P<0.001）；D-Pro为1.29±0.27（n = 4），L-Pro为0.30±0.14（n = 9）（P<0.001）。注射D-顺式-FPro后（n = 3）对大鼠脑组织的分析显示，蛋白质中无放射性，但有相当一部分以L-反式-FPro的形式存在。PET研究表明，在人类皮质中，D-顺式-FPro的SUV和流入速率常数比L-顺式-FPro高4至5倍。我们得出结论，与它们的L型异构体相比，D-顺式-FPro和D-Pro在血脑屏障处更易被转运，并在脑内异构化为L型。因此，血浆中的D-Pro可能是脑内L-脯氨酸的一个来源，L-脯氨酸已被证明可作为兴奋性神经传递的调节剂。
