Carrier-mediated transport of enkephalins and N-Tyr-MIF-1 across blood-brain barrier
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.
- Research Organization:
- Veterans Administration Medical Center, New Orleans, LA
- OSTI ID:
- 7188111
- Journal Information:
- Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States)
- Country of Publication:
- United States
- Language:
- English
Similar Records
Stereospecific transport of Tyr-MIF-1 across the blood-brain barrier by peptide transport system-1
Differential effect of aluminum on the blood-brain barrier transport of peptides, technetium and albumin
Related Subjects
BLOOD-BRAIN BARRIER
MEMBRANE TRANSPORT
ENKEPHALINS
BRAIN
CARRIERS
IODINE 125
LABELLED COMPOUNDS
MICE
PEPTIDES
TECHNETIUM 99
TRACER TECHNIQUES
TYROSINE
AMINO ACIDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENDORPHINS
HOURS LIVING RADIOISOTOPES
HYDROXY ACIDS
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
POLYPEPTIDES
PROTEINS
RADIOISOTOPES
RODENTS
TECHNETIUM ISOTOPES
VERTEBRATES
YEARS LIVING RADIOISOTOPES
551001* - Physiological Systems- Tracer Techniques