title: Aluminum citrate is transported from brain into blood via the monocarboxylic acid transporter located at the blood-brain barrier.
abstract: Aluminum citrate transport across the blood-brain barrier was assessed in rats by in vivo microdialysis. Microdialysis probes were implanted in the jugular vein as well as the left and right frontal cortex. It was demonstrated previously (Allen et al., 1995), in this study, that the steady-state aluminum citrate brain-to-blood-ratio (BBr) is less than 1, suggesting the presence of a process other than diffusion. The addition of 2,4-dinitrophenol (10 microM) to the dialysate perfusing a microdialysis probe in the brain increased the steady-state aluminum citrate brain-to-blood-ratio to a value (1.14) not significantly different from 1, suggesting the presence of an active transporter that is blocked by the metabolic inhibitor. The addition of valproic and pyruvic acid, as putative and known substrates for the monocarboxylic acid transporter, respectively, to brain dialysate (10 and 100 mM) had different outcomes. Valproic acid was ineffective at either concentration, whereas pyruvic acid (100 mM) significantly increased the aluminum citrate brain-to-blood-ratio from 0.19 to 0.31. Pyruvic acid (1 M in the dialysate) increased the aluminum citrate brain-to-blood-ratio to a value not different from unity, suggesting competition between aluminum citrate and pyruvic acid for transport. The only energy-dependent, pyruvic acid-inhibitable transporter is the monocarboxylic acid transporter. Theoretical, pharmacokinetic modeling suggests that the transporter producing an aluminum citrate brain-to-blood-ratio less than 1 is predominantly located at the blood-brain barrier, rather than at neuronal or glial cell membranes. We propose that the monocarboxylic acid transporter at the blood-brain barrier maintains a steady-state aluminum citrate brain-to-blood-ratio much less than 1.
authors.affiliation: College of Pharmacy, University of Kentucky, Lexington 40536-0082, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Ackley
authors.forename: R A
authors.initials: RA
authors.lastname: Yokel
mesh_terms: D019297:2,4-Dinitrophenol / Q000737:chemistry / Q000378:metabolism; D000535:Aluminum / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier; D002851:Chromatography, High Pressure Liquid; D019343:Citric Acid / Q000097:blood / Q000493:pharmacokinetics*; D015314:Dialysis Solutions; D004058:Diffusion; D007601:Jugular Veins / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D019289:Pyruvic Acid / Q000097:blood / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014635:Valproic Acid / Q000097:blood / Q000378:metabolism
chemical_list: D015314:Dialysis Solutions; D000644:Quaternary Ammonium Compounds; D019343:Citric Acid; C079419:4-trimethylammoniumantipyrine; D014635:Valproic Acid; D019289:Pyruvic Acid; D000535:Aluminum; D019297:2,4-Dinitrophenol; D000983:Antipyrine