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Setting-up an In Vitro Model of Rat Blood-brain Barrier (BBB): A Focus on BBB Impermeability and Receptor-mediated Transport
Published on: June 28, 2014
Blood-brain barrier transport of L-tyrosine Conjugates: a model study for the brain targeting using large neutral
T Ohnishi1, T Maruyama, S Higashi
1Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Science. Horinouchi 1432-1, Hachiouji, Tokyo 192-0329, Japan. ohnishi2ps.toyaku.ac.jp
Abstract:
We examined the relation ship between the charge of the amino or carboxylic function of a substrate and the substrate recognition by the large neutral amino acid (LNAA) transport carrier, using the in situ brain perfusion technique. Glucose-coupled L-tyrosine (GcpY), which has a free carboxylic function, and 2-(L-tyrosylamide)-2-deoxy-D-glucose (Y-2DG), which has a free amino function were synthesized. The inhibitory effect of GcpY on [3 H]L-tyrosine uptake was larger than that of N-methly-L-phenylalanine or N-acetyl-L-phenylalanine, whereas Y-2DG did not affect it. These results indicate that a free amino group is not required for recognition, provided that the modified amino group is able to take a positive charge. Steric factors appeared to be relatively unimportant.
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