Stereospecific transport of Tyr-MIF-1 across the blood-brain barrier by peptide transport system-1.
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.
Banks
W A
WA
Veterans Affairs Medical Center, New Orleans, LA.
Kastin
A J
AJ
Michals
E A
EA
Barrera
C M
CM
D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology*; D007276:Injections, Intraventricular; D007457:Iodine Radioisotopes; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013667:Technetium
D007457:Iodine Radioisotopes; D010455:Peptides; D013667:Technetium; C036930:tyrosyl-prolyl-leucyl-glycinamide; D009075:MSH Release-Inhibiting Hormone