Aging and the blood-brain barrier: changes in the carrier-mediated transport of peptides in rats

Abstract

Age-related changes in the brain's saturable, specific, carrier-mediated transport system for the small, N-tyrosinated peptides Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) and methionine-enkephalin (Met-Enk) were studied in Fischer 344 rats aged 4 and 26 months. These studies showed statistically significant differences between the two age groups for both the Tmax (transport maximum) [3.22 +/- 0.013 nmol/min/g (young rats, mean +/- S.E.M.) vs 2.41 +/- 0.009 nmol/min/g (age rats)] and T50 (the amount required to achieve 50% of that maximum) [84.9 +/- 1.0 nmol/g (young) vs 65.1 +/- 0.60 nmol/g (aged)]. The T50:Tmax ratio was nearly equal to the two groups: 26.4 (young) vs 26.9 (aged), consistent with the uncompetitive type of inhibition indicative of alterations in the substrate-carrier complex. In addition, blood concentrations of Tyr-MIF-1-like immunoactivity were nearly doubled in aged rats (3.24 +/- 0.373 vs 1.67 +/- 0.0904 pM/ml), while blood concentrations of Met-Enk-like immunoactivity and brain concentrations of immunoactive Tyr-MIF-1 and Met-Enk showed no statistically significant difference between age groups. Thus, a carrier-mediated system responsible for the transport of peptides across the blood-brain barrier undergoes changes with aging.