Transport of 5-aminolevulinic acid between blood and brain

Little is known about the movement of 5-aminolevulinic acid (delta-aminolevulinic acid; ALA) between blood and brain. This is despite the fact that increases in brain ALA may be involved in generating the neuropsychiatric symptoms in porphyrias and that systemic administration of ALA is currently being used to delineate the borders of malignant gliomas. The current study examines the mechanisms involved in the movement of [(14)C]ALA across the blood-brain and blood-CSF barriers in the rat. In the adult rat, the influx rate constant (K(i)) for [(14)C]ALA movement into brain was low ( approximately 0.2 microl/g per min), was unaffected by increasing plasma concentrations of non-radioactive ALA or probenecid (an organic anion transport inhibitor) and, therefore, appears to be a diffusional process. The K(i) for [(14)C]ALA was 3-fold less than that for [(14)C]mannitol, a molecule of similar size. This difference appears to result from a lower lipid solubility rather than saturable [(14)C]ALA transport from brain to blood. The K(i) for [(14)C]ALA for uptake into the neonatal brain was 7-fold higher than in the adult. However, again, this was unaffected by increasing plasma ALA concentrations suggesting a diffusional process. In contrast, at the blood-CSF barrier, there was evidence of carrier-mediated [(14)C]ALA transport from blood to choroid plexus and blood to CSF. Both processes were inhibited by administration of non-radioactive ALA and probenecid. However, experiments in choroid plexus epithelial cell primary cultures indicated that transport in these cells was polarized with [(14)C]ALA uptake from the apical (CSF) side being about 7-fold greater than uptake from the basolateral (blood) side. In total, these results suggest that the brain is normally fairly well protected from changes in plasma ALA concentration by the very low blood-brain barrier permeability of this compound and by a saturable efflux mechanism present at the choroid plexus.