title: pH dependence of histidine affinity for blood-brain barrier carrier transport systems for neutral and cationic amino acids.
abstract: 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.
authors.affiliation: Research Service, Veterans Administration Medical Center, Brentwood, Los Angeles, CA 90073.
authors.forename: W H
authors.initials: WH
authors.lastname: Oldendorf
authors.forename: P D
authors.initials: PD
authors.lastname: Crane
authors.forename: L D
authors.initials: LD
authors.lastname: Braun
authors.forename: E A
authors.initials: EA
authors.lastname: Gosschalk
authors.forename: J M
authors.initials: JM
authors.lastname: Diamond
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier; D002352:Carrier Proteins / Q000378:metabolism*; D002412:Cations / Q000378:metabolism; D005260:Female; D006639:Histidine / Q000378:metabolism*; D006859:Hydrogen / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000596:Amino Acids; D002352:Carrier Proteins; D002412:Cations; D006639:Histidine; D006859:Hydrogen