Blood-brain barrier transport of L-tyrosine Conjugates: a model study for the brain targeting using large neutral amino acid transport system.
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.
Ohnishi
T
T
Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Science. Horinouchi 1432-1, Hachiouji, Tokyo 192-0329, Japan. ohnishi2ps.toyaku.ac.jp
Maruyama
T
T
Higashi
S
S
Awazu
S
S
D026905:Amino Acid Transport Systems; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D005947:Glucose / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*
D026905:Amino Acid Transport Systems; D002352:Carrier Proteins; D014443:Tyrosine; D005947:Glucose