In vitro penetration of des-tyrosine1-D-phenylalanine3-beta-casomorphin across the blood-brain barrier.
The blood-brain barrier transport and metabolism of the synthetic beta-casomorphin (beta CM) derivative des-tyrosine1-D-phenylalanine3-beta-casomorphin (DT-D-Phe3-beta CM) were investigated using an in vitro model consisting of primary cultures of bovine cerebrovascular endothelial cells. DT-D-Phe3-beta CM was transported across the endothelial monolayer without significant metabolism. The endothelial permeability expressing the transport rate ranged between 1.4 and 2.2 cm x 10(-3)/min and was neither affected by luminal concentration changes (1 nM and 1 microM) nor different after luminal and abluminal administration. The metabolic inhibitor 2-desoxy-D-glucose did not affect the permeability of DT-D-Phe3-beta CM. These results suggest that DT-D-Phe3-beta CM is able to cross the blood-brain barrier by paracellular transport without using a carrier system.
Stark
H
H
Center for Bio-Pharmaceutical Sciences, State University of Leiden, The Netherlands.
Van Bree
J B
JB
de Boer
A G
AG
Jaehde
U
U
Breimer
D D
DD
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000494:pharmacology; D004723:Endorphins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D008657:Metabolic Clearance Rate; D010446:Peptide Fragments / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects
D004723:Endorphins; D010446:Peptide Fragments; C059556:beta-casomorphin, des-Tyr-; D003847:Deoxyglucose