Transport of leucine-enkephalin across the blood-brain barrier in the perfused guinea pig brain

• Published in: Journal of neurochemistry Vol. 49; no. 1; p. 310
• Main Authors: Zloković, B V, Lipovac, M N, Begley, D J, Davson, H, Rakić, L
• Format: Journal Article
• Language: English
• Published: England 01.07.1987
• Subjects: Bacitracin - pharmacology; Blood-Brain Barrier; Brain - metabolism; Caudate Nucleus - metabolism; Enkephalin, Leucine - metabolism; Female; Hippocampus - metabolism; Kinetics; Male; Naloxone - pharmacology; Parietal Lobe - metabolism; Tyrosine - pharmacology
• ISSN: 0022-3042
• DOI: 10.1111/j.1471-4159.1987.tb03431.x

Transport of [tyrosyl-3,5-3H]enkephalin-(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 (Kin) estimated from the multiple-time uptake data for [3H]Leu-enkephalin ranged from 3.62 X 10(-3) to 3.63 X 10(-3) ml min-1 g-1 in 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 (1 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.