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Transport and distribution of homocarnosine after intracerebroventricular and intravenous injection in the rat

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Abstract

Rats were injected intracerebroventricularly (i.c.v.) or i.v. with [14C]homocarnosine (250 nmol). Distribution of the dipeptide in brain structures, transport from the brain to the blood, distribution in peripheral organs, and excretion in the urine were studied by measuring radioactivity in tissue, plasma, and urine samples by liquid scintillation counting 15–120 min after injection. After i.c.v. injection, [14C]homocarnosine was taken up into all parts of the brain investigated (highest uptake in structures close to the site of injection), it was transported to the blood, and radioactive substances were found in low concentration in muscle, spleen, and liver, in high concentration in the kidneys, and very high concentration in the urine. Investigations using high pressure liquid chromatography (HPLC) showed that no degradation took place in the brain, all radioactivity was found in the homocarnosine fraction. In the plasma 86% of the radioactivity was found in the GABA fraction presumed to be formed by cleavage of the peptide, while in the kidneys 35% and in the urine 40% was found in the GABA fraction. After i.v. injection of [14C]homocarnosine, no radioactivity was measured in hippocampus, striatum, cerebellum and cerebral cortex 15 min after injection, however, 60 min after injection a very low activity was detected in these structures (estimated intravascular radioactivity subtracted). A low activity was also measured in the spinal cord both 15 and 60 min after injection. When homocarnosine and GABA were separated on HPLC, all radioactivity in brain tissue was found in the GABA fraction, indicating either that [14C]homocarnosine did not cross the blood-brain barrier in amounts that could be measured with the method used, or that peptide entering the brain was rapidly transported back to the blood. [14C]Homocarnosine was not taken up either into crude synaptosomal preparations from hippocampus, striatum, cerebellum, cortex and spinal cord, or into slices prepared from the hippocampus and striatum. Transport from the brain to the kidneys and excretion in the urine seems to be a major route for disposal of this peptide in the rat.

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Authors and Affiliations

  1. Department of Physiology, University of Bergen, Arstadveien 19, N-5000, Bergen, Norway

    Kjell Hole M.D. & Ida Haugan

  2. Institute of Medical Genetics, University of Oslo, Blindern, Oslo, Norway

    Øyvind Ziesler & Anne-Lise Børresen

  3. Central Laboratory, Dikemark Hospital, N-1370, Asker, Norway

    Leiv R. Gjessing

  4. Department of Neurology, Trondheim University Hospital, N-7000, Trondheim, Norway

    Ottar Sjaastad

Authors
  1. Øyvind Ziesler
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  2. Kjell Hole M.D.
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  3. Ida Haugan
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  4. Anne-Lise Børresen
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  5. Leiv R. Gjessing
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  6. Ottar Sjaastad
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Ziesler, Ø., Hole, K., Haugan, I. et al. Transport and distribution of homocarnosine after intracerebroventricular and intravenous injection in the rat. Neurochem Res 9, 637–648 (1984). https://doi.org/10.1007/BF00964510

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  • DOI: https://doi.org/10.1007/BF00964510

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