Leucine-enkephalin metabolism in brain microvessel endothelial cells.
The metabolism of leucine-enkephalin was investigated in primary cultures of bovine brain microvessel endothelial cell (BMEC) monolayers. Leucine-enkephalin was hydrolyzed slowly with less than 40% of the peptide metabolized following a 5-h incubation with intact BMEC monolayers at 37 degrees C. Following separation and extraction of BMEC enzymes into cytosolic and membrane-bound fractions, leucine-enkephalin was observed to be labile in the presence of both cytosolic and membrane-associated enzymes. A much greater concentration of enkephalin-hydrolyzing enzyme was associated with the cytosolic fraction. Resulting metabolite profiles for leucine-enkephalin appeared to be the result of interactions of the peptide with primarily aminopeptidases and angiotensin-converting enzyme. Our results suggested that extensive metabolism of leucine-enkephalin solely by BMECs in the cerebro-vasculature would require internalization by the cells and presentation to cytosolic enzymes.
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045.
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Thompson
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Audus
D000818:Animals; D001921:Brain / Q000098:blood supply*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004743:Enkephalin, Leucine / Q000378:metabolism*
D004743:Enkephalin, Leucine