The Effect of Glycosylation on the Uptake of an Enkephalin Analogue into the Central Nervous System

  • Sarah A. Williams
  • Thomas J. Abbruscato
  • Lajos Szabo
  • Robin Polt
  • Victor Hruby
  • Thomas P. Davis
Part of the Advances in Behavioral Biology book series (ABBI, volume 46)


In contrast to unglycosylated controls, glycosylated [D-Cys2,5]enkephalin-ser-gly (glycosylated DCDCE-ser-gly) elicits analgesia after intraperitoneal administration. This was postulated to be due to the presence of the glucose moiety allowing the analogue to cross the BBB via the glucose carrier. To test this hypothesis, the present study investigated the biological stability and the CNS uptake ofunglycosylated and glycosylated DCDCE-ser-gly. Interestingly, the metabolic half-lives and ability to cross the in vitro BBB was found to be similar for both analogues. In situ brain perfusion indicated that the brain uptake of glycosylated DCDCE-ser-gly was greater than that for the vascular marker, [14C]sucrose, but similar to the CSF uptake of the peptide. CNS uptake of glycosylated DCDCE-ser-gly was not affected by replacing D- with L- glucose, nor with the addition of 10 µM unlabelled glycosylated DCDCE-ser-gly. In summary, the difference in analgesic response of glycosylated compared to unglycosylated DCDCE-ser-gly, is not related to either differing metabolic profiles, nor the ability of the glycosylated analogue to use the glucose carrier to enter the CNS. However, this study does not eliminate the involvement of a different low affinity, saturable uptake system taking the glycosylated, but not the unglycosylated form.


Permeability Coefficient Brain Perfusion Brain Uptake Perfusion Medium Brain Microvessel Endothelial Cell 


Après administration par voie intrapéritonéale, le peptide glycosylé (D-cys 2,5)enképhaline-ser-gly (DCDCE-ser-gly) montre une activité analgésique, contrairement au même peptide non-glycosylé. L’effet pharmacologique spécifique de l’enképhaline glycosylée pourrait être expliqué par l’addition du radical glycosylé qui permettrait àl’enképhaline de traverser la barrière hémato-encéphalique (BHE) en utilisant le transporteur du glucose. Afin de vérifier cette hypothèse, la stabilité ainsi que la pénétration cérébrale des molécules glycosylées et non glycosylées ont été étudiées. La demi-vie métabolique et la perméabilité de la BHE pour ces deux composés est semblable. Des études de microdialyse dans le cerveau montrent que la capture cérébrale du dérivé glycosylé est superieure à celle du (14 C)sucrose, mais similaire àla capture du peptide par le liquide cérébro-spinal. De plus, la capture cérébrale de la molécule glycosylée marquée n'est pas inhibée par le remplacement du D-glucose par du L-glucose ni par la dilution de la molécule marquée avec 10mM d'enképhaline glycosylée non marquée. En conséquence, les différences de réponse analgésique observées entre la DCDCE glycosylée et non glycosylée ne sont pas liées à une plus grande stabilité de la molécule glycosylée, ni au transport spécifique de ce composé par le transporteur du glucose de la BHE. Cependant cette étude n'écarte pas la possibilité du transport specifique du dérivé glycosylé par un autre système de transport saturable à faible affinité.


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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Sarah A. Williams
    • 1
  • Thomas J. Abbruscato
    • 1
  • Lajos Szabo
    • 2
  • Robin Polt
    • 2
  • Victor Hruby
    • 2
  • Thomas P. Davis
    • 1
  1. 1.Department of PharmacologyUniversity of ArizonaTucsonUSA
  2. 2.Department of ChemistryUniversity of ArizonaTucsonUSA

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