Compartmentation in amino acid transport across the blood brain barrier.
Under steady-state conditions, the transport rates for amino acids from blood to brain have been found to be about half that seen using the intraarterial injection technique. Using a method that mathematically mimics the constant infusion procedure, we were able to reconcile this apparent discrepancy. At less than 1 min after subcutaneous injection of [14C]tyrosine in mice, we have observed a rate of entry into brain of 19.7 nmol/g/min, while from 1-15 min we have measured the rate at 6.4 nmol/g/min. Using methionine sulfoximine as an inhibitor of the gamma-glutamyl cycle, the early rate was reduced to 10.0 nmol/g/min and the later rate to 3.7 nmol/g/min. These data are consistent with a two-compartment system regulating amino acid transport into the neurons. A mathematical model fit to these data indicates that the first compartment contains 8.3 nanomoles of tyrosine per gram brain or about 6.7% of the brain total. It is speculated that the first compartment consists primarily of the astrocytes.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier; D007279:Injections, Subcutaneous; D008717:Methionine Sulfoximine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D014443:Tyrosine / Q000008:administration & dosage / Q000378:metabolism*
D008717:Methionine Sulfoximine; D014443:Tyrosine