AJP - Endocrinology and Metabolism, Vol 251, Issue 4 477-E482, Copyright © 1986 by American Physiological Society

ARTICLES

Carrier-mediated transport of enkephalins and N-Tyr-MIF-1 across blood-brain barrier

W. A. Banks, A. J. Kastin, A. J. Fischman, D. H. Coy and S. L. Strauss

The saturable, carrier-mediated system capable of the brain-to-blood transport of small peptides with an N-terminal tyrosine was characterized. The rate of disappearance of intraventricularly injected iodinated peptide in the presence or absence of the inhibitor being tested was determined from formulas based on the residual radioactivity in the brains of mice after decapitation. The injection of 100 nmol/mouse of unlabeled N-Tyr-MIF-1 (TMIF) increased the half-time disappearance of 125I-TMIF (ITMIF) in the central nervous system (CNS) from 14.1 to 88.7 min (P less than 0.00005). Technetium, a substance transported out of the brain by the same system that transports iodine, was used as a control; the half-time disappearance of technetium pertechnetate was unaffected by unlabeled TMIF. With two related but distinct techniques, the maximum transport rate out of the CNS (Vmax) for TMIF was 0.266 nmol X g of brain per min (method 1) and 0.297 nmol X g-1 X min-1 (method 2), while the amount of unlabeled material needed to achieve 50% of Vmax (Km) was 15.2 nmol/g (method 1) and 15.1 nmol/g (method 2). The lack of effect of the tyrosinated fragments of TMIF as inhibitors indicates that TMIF is being transported in intact form. The Vmax for methionine enkephalin determined with labeled and unlabeled methionine enkephalin was 0.630 nmol X g-1 X min-1 and the Km was 24.95 nmol/g. Studies with the metabolic modulators furosemide, acetozolamide, reserpine, ouabain, and theophylline suggest that the system is sodium dependent and probably independent of ATPase.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				A. J. Kastin, M. B. Fasold, and J. E. Zadina Endomorphins, Met-Enkephalin, Tyr-MIF-1, and the P-glycoprotein Efflux System Drug Metab. Dispos., March 1, 2002; 30(3): 231 - 234. [Abstract] [Full Text] [PDF]

				W. A. Banks, S. A. Farr, W. Butt, V. B. Kumar, M. W. Franko, and J. E. Morley Delivery across the Blood-Brain Barrier of Antisense Directed against Amyloid beta : Reversal of Learning and Memory Deficits in Mice Overexpressing Amyloid Precursor Protein J. Pharmacol. Exp. Ther., June 1, 2001; 297(3): 1113 - 1121. [Abstract] [Full Text]

				C. Rousselle, M. Smirnova, P. Clair, J.-M. Lefauconnier, A. Chavanieu, B. Calas, J.-M. Scherrmann, and J. Temsamani Enhanced Delivery of Doxorubicin into the Brain via a Peptide-Vector-Mediated Strategy: Saturation Kinetics and Specificity J. Pharmacol. Exp. Ther., January 1, 2001; 296(1): 124 - 131. [Abstract] [Full Text]

				M. Hauser, A. M. Donhardt, D. Barnes, F. Naider, and J. M. Becker Enkephalins Are Transported by a Novel Eukaryotic Peptide Uptake System J. Biol. Chem., February 4, 2000; 275(5): 3037 - 3041. [Abstract] [Full Text] [PDF]

				G. Roman, V. Meller, K. H. Wu, and R. L. Davis The opt1 gene of Drosophila melanogaster encodes a proton-dependent dipeptide transporter Am J Physiol Cell Physiol, September 1, 1998; 275(3): C857 - C869. [Abstract] [Full Text] [PDF]