Kinetic analysis of leucine-enkephalin cellular uptake at the luminal side of the blood-brain barrier of an in situ perfused guinea-pig brain. 1989

B V Zlokovic, and J B Mackic, and B Djuricic, and H Davson
Department of Medical Physiology, Faculty of Medicine Belgrade, Yugoslavia.

The uptake of enkephalin-(5-L-leucine) (Leu-enkephalin) at the luminal side of the blood-brain barrier was measured by means of an in situ vascular brain perfusion technique in the anaesthetized guinea pig. This method allows measurements of cerebrovascular peptide uptake over periods of up to 20 min, and excludes the solute under study from the general circulation and systemic metabolic influences. A capillary unidirectional transfer constant, Kin, for [tyrosyl-3,5-3H]Leu-enkephalin was estimated graphically from the multiple-time brain uptake data in the presence of different concentrations of unlabelled peptide, and dose-dependent self-inhibition was demonstrated. Analysis of unidirectional influx of blood-borne Leu-enkephalin into the brain revealed Michaelis-Menten saturation kinetics in the parietal cortex, caudate nucleus, and hippocampus, with Vmax between 0.14 and 0.16 nmol min-1 g-1 and Km ranging from 34 to 41 microM, for the saturable component, whereas the estimated diffusion constant, Kd, was not significantly different from zero. Entry of [3H]Leu-enkephalin was not inhibited in the presence of either a 5 mM concentration of unlabelled L-tyrosine, tyrosylglycine, and tyrosylglycylglycine, or aminopeptidase inhibitor, bestatin (0.5 mM), suggesting that the saturable mechanism of the tracer at the luminal side of the blood-brain barrier does not involve uptake of the peptide's N-terminal amino acid and/or its tyrosine-containing fragments.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010296 Parietal Lobe Upper central part of the cerebral hemisphere. It is located posterior to central sulcus, anterior to the OCCIPITAL LOBE, and superior to the TEMPORAL LOBES. Brodmann Area 39,Brodmann Area 40,Brodmann Area 5,Brodmann Area 7,Brodmann's Area 39,Brodmann's Area 40,Brodmann's Area 5,Brodmann's Area 7,Inferior Parietal Cortex,Secondary Sensorimotor Cortex,Superior Parietal Lobule,Angular Gyrus,Gyrus Angularis,Gyrus Supramarginalis,Intraparietal Sulcus,Marginal Sulcus,Parietal Cortex,Parietal Lobule,Parietal Region,Posterior Paracentral Lobule,Posterior Parietal Cortex,Praecuneus,Precuneus,Precuneus Cortex,Prelunate Gyrus,Supramarginal Gyrus,Area 39, Brodmann,Area 39, Brodmann's,Area 40, Brodmann,Area 40, Brodmann's,Area 5, Brodmann,Area 5, Brodmann's,Area 7, Brodmann,Area 7, Brodmann's,Brodmanns Area 39,Brodmanns Area 40,Brodmanns Area 5,Brodmanns Area 7,Cortex, Inferior Parietal,Cortex, Parietal,Cortex, Posterior Parietal,Cortex, Precuneus,Cortex, Secondary Sensorimotor,Cortices, Inferior Parietal,Gyrus, Angular,Gyrus, Prelunate,Gyrus, Supramarginal,Inferior Parietal Cortices,Lobe, Parietal,Lobule, Parietal,Lobule, Posterior Paracentral,Lobule, Superior Parietal,Paracentral Lobule, Posterior,Paracentral Lobules, Posterior,Parietal Cortex, Inferior,Parietal Cortex, Posterior,Parietal Cortices,Parietal Cortices, Inferior,Parietal Cortices, Posterior,Parietal Lobes,Parietal Lobule, Superior,Parietal Lobules,Parietal Lobules, Superior,Parietal Regions,Posterior Paracentral Lobules,Posterior Parietal Cortices,Precuneus Cortices,Region, Parietal,Secondary Sensorimotor Cortices,Sensorimotor Cortex, Secondary,Superior Parietal Lobules
D010477 Perfusion Treatment process involving the injection of fluid into an organ or tissue. Perfusions
D001812 Blood-Brain Barrier Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue. Brain-Blood Barrier,Hemato-Encephalic Barrier,Barrier, Blood-Brain,Barrier, Brain-Blood,Barrier, Hemato-Encephalic,Barriers, Blood-Brain,Barriers, Brain-Blood,Barriers, Hemato-Encephalic,Blood Brain Barrier,Blood-Brain Barriers,Brain Blood Barrier,Brain-Blood Barriers,Hemato Encephalic Barrier,Hemato-Encephalic Barriers
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002196 Capillaries The minute vessels that connect arterioles and venules. Capillary Beds,Sinusoidal Beds,Sinusoids,Bed, Sinusoidal,Beds, Sinusoidal,Capillary,Capillary Bed,Sinusoid,Sinusoidal Bed
D004743 Enkephalin, Leucine One of the endogenous pentapeptides with morphine-like activity. It differs from MET-ENKEPHALIN in the LEUCINE at position 5. Its first four amino acid sequence is identical to the tetrapeptide sequence at the N-terminal of BETA-ENDORPHIN. Leucine Enkephalin,5-Leucine Enkephalin,Leu(5)-Enkephalin,Leu-Enkephalin,5 Leucine Enkephalin,Enkephalin, 5-Leucine,Leu Enkephalin
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums

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