In vitro penetration of des-tyrosine1-D-phenylalanine3-β-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.