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Transport of Leucine-Enkephalin Across the Blood-Brain Barrier in the Perfused Guinea Pig Brain


  • The permanent address of Dr. D. J. Begley and Dr. H. Davson is The Department of Physiology, King's College London, Strand, London WC2R 2LS, U.K.

  • The permanent address of Dr. Lj. Rakić is Department of Biochemistry, Faculty of Medicine, Belgrade, Yugoslavia.

Address correspondence and reprint requests to Dr. B. V. Zloković at Department of Medical Physiology, Faculty of Medicine Belgrade, Belgrade, Yugoslavia.


Abstract: Transport of [tyrosyl-3, 5−3H]enkephaIin-(5-L-leucine) ([3H]Leu-enkephalin) across the blood-brain barrier was studied in the adult guinea pig, by means of vascular perfusion of the head in vivo. The unidirectional transfer constant (Kim) estimated from the multiple-time uptake data for [3H]Leu-enkephalin ranged from 3.62 ± 10−3 to 3.63 ± 10−3 ml min−1 g−1in the parietal cortex, caudate nucleus, and hippocampus. Transport of [3H]Leu-enkephalin was not inhibited by unlabelled L-tyrosine (the N-terminal amino acid) at a concentration as high as 5 mM, or by the inhibitor of aminopeptidase activity bacitracin (2 mM), suggesting that there was no enzymatic degradation of peptide at the blood-brain barrier. By contrast, 2 mM unlabelled Leu-enkephalin strongly inhibited the unidirectional blood-to-brain transport of [3H]Leu-enkephalin by 74-78% in the parietal cortex, caudate nucleus, and hippocampus. The tetrapeptide tyrosyl-glycyl-glycyl-phenylalanine (without the C-terminal leucine of Leu-enkephalin), at a concentration of 5 mM, caused a moderate inhibition ranging from 15 to 29% in the brain regions studied, whereas the tetrapeptide glycyl-glycyl-phenylalanyl-leucine (without the N-terminal tyrosine) at 5 mM was without effect on Leu-enkephalin transport. Unidirectional brain uptake of Leu-enkephalin was not altered in the presence of naloxone at a concentration as high as 3 mM(I mg/ml), suggesting that there is no binding of Leu-enkephalin to opioid receptors at the blood-brain barrier. It is concluded that there is a specific transport mechanism for Leu-enkephalin at the blood-brain barrier in the guinea pig.