Differential effect of aluminum on the blood-brain barrier transport of peptides, technetium and albumin.
Aluminum is a neurotoxin capable of altering membrane structure and function. We investigated whether aluminum also can affect saturable transport across membranes using the blood-brain barrier as our model. Mice were given i.p. or i.v. aluminum (up to 100 mg/kg) as the chloride salt and the disappearance from the brain of several centrally administered substances was measured. We found that aluminum rapidly and profoundly inhibited the saturable system that transports the small, N-tyrosinated peptides Tyr-MIF-1 and the enkephalins from the brain to the blood by acting as a noncompetitive inhibitor. In contrast, the disappearance from the brain of technetium pertechnetate (a substance also transported out of the brain by a different saturable system), albumin or D-Tyr-MIF-1 (a stereoisomer of Tyr-MIF-1 that was confirmed not to be transported by the carrier system) was not affected by aluminum. Aluminum also did not alter either the saturable or nonsaturable component of the uptake of Tyr-MIF-1 by erythrocytes. These findings suggest that one mechanism by which aluminum may induce neurotoxicity is by selective alteration of the transport systems of the blood-brain barrier.
D000418:Albumins / Q000493:pharmacokinetics*; D000535:Aluminum / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004745:Enkephalins / Q000493:pharmacokinetics; D004912:Erythrocytes / Q000378:metabolism; D007700:Kinetics; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013667:Technetium / Q000493:pharmacokinetics*
D000418:Albumins; D004745:Enkephalins; D013667:Technetium; C036930:tyrosyl-prolyl-leucyl-glycinamide; D009075:MSH Release-Inhibiting Hormone; D000535:Aluminum