Oldendorf W H, Crane P D, Braun L D, Gosschalk E A, Diamond J M
Research Service, Veterans Administration Medical Center, Brentwood, Los Angeles, CA 90073.
J Neurochem. 1988 Mar;50(3):857-61. doi: 10.1111/j.1471-4159.1988.tb02991.x.
The effects of pH (3.5-7.5) on the brain uptake of histidine by the blood-brain barrier (BBB) carriers for neutral and cationic amino acids were tested, in competition with unlabeled histidine, arginine, or phenylalanine, with the single-pass carotid injection technique. Cationic amino acid ( [14C]arginine) uptake was increasingly inhibited by unlabeled histidine as the pH of the injection solution decreased. In contrast, the inhibitory effect of unlabeled histidine on neutral amino acid ( [14C]phenylalanine) uptake decreased with decreasing pH. Brain uptake indices with varying histidine concentrations indicated that the neutral form of histidine inhibited phenylalanine uptake whereas the cationic form competed with arginine uptake. Since phenylalanine decreased [14C]histidine uptake at all pH values whereas arginine did not, it was concluded that the cationic form of histidine had an affinity for the cationic carrier, but was not transported by it. We propose that the saturable entry of histidine into brain is, under normal physiological circumstances, mediated solely by the carrier for neutral amino acids.
采用单通道颈动脉注射技术，在与未标记的组氨酸、精氨酸或苯丙氨酸竞争的情况下，测试了pH值（3.5 - 7.5）对血脑屏障（BBB）中中性和阳离子氨基酸载体摄取组氨酸进入大脑的影响。随着注射溶液pH值降低，未标记的组氨酸对阳离子氨基酸（[14C]精氨酸）摄取的抑制作用逐渐增强。相反，未标记的组氨酸对中性氨基酸（[14C]苯丙氨酸）摄取的抑制作用随pH值降低而减弱。不同组氨酸浓度下的脑摄取指数表明，组氨酸的中性形式抑制苯丙氨酸摄取，而阳离子形式与精氨酸摄取竞争。由于苯丙氨酸在所有pH值下均降低[14C]组氨酸摄取，而精氨酸则不然，因此得出结论，组氨酸的阳离子形式对阳离子载体具有亲和力，但不能被其转运。我们提出，在正常生理情况下，组氨酸进入大脑的可饱和转运仅由中性氨基酸载体介导。
