INVITRO PENETRATION OF ES-TYROSINE(1)-D-PHENYLALANINE(3)-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 mo del consisting of primary cultures of bovine cerebrovascular endotheli al cells. DT-D-Phe3-beta-CM was transported across the endothelial mon olayer without significant metabolism. The endothelial permeability ex pressing 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 -mu-M) nor different after luminal and abluminal administration. The m etabolic 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 withou t using a carrier system.