Stereospecific transport of Tyr-MIF-1 across the blood-brain barrier by peptide transport system-1

• Published in: Brain research bulletin Vol. 25; no. 4; p. 589
• Main Authors: Banks, W A, Kastin, A J, Michals, E A, Barrera, C M
• Format: Journal Article
• Language: English
• Published: United States 01-10-1990
• Subjects: Animals; Biological Transport, Active - physiology; Blood-Brain Barrier - physiology; Injections, Intraventricular; Iodine Radioisotopes; Male; Mice; Mice, Inbred ICR; MSH Release-Inhibiting Hormone - analogs & derivatives; MSH Release-Inhibiting Hormone - metabolism; Peptides - metabolism; Rats; Rats, Inbred Strains; Stereoisomerism; Technetium
• ISSN: 0361-9230
• DOI: 10.1016/0361-9230(90)90116-H

Previous studies have suggested that peptide transport system-1 (PTS-1), the saturable system that transports Tyr-MIF-1, the enkephalins, and related peptides out of the central nervous system (CNS), exhibits stereospecificity. In the present studies, we showed that 125I-L-Tyr-MIF-1, but not 131I-D-Tyr-MIF-1, was cleared from the CNS more rapidly than could be accounted for by nonspecific mechanisms. Such clearance was inhibited by a 1.0 nmol dose of L-Tyr-MIF-1, but not by D-Tyr-MIF-1. Neither L- nor D-Tyr-MIF-1 altered the much lower clearance of I-D-Tyr-MIF-1 from the brain. Radioactivity recovered from the vascular space after the injection of 125I-Tyr-MIF-1 into the lateral ventricle of the brain eluted by HPLC primarily as intact peptide, demonstrating that most of the Tyr-MIF-1 was not degraded during transport. By contrast, the nonsaturable unidirectional influx of Tyr-MIF-1 into the CNS did not distinguish between the isomers. These studies confirm and extend the observations that Tyr-MIF-1 is transported out of the CNS by a saturable, stereospecific transport system as an intact peptide while the influx into the CNS is by a nonsaturable mechanism that does not distinguish between the isomers.