Effect of the cationic polypeptide polylysine on neutral amino acid transport in isolated brain microvessels

The functionality of isolated brain microvessels - used as anin vitro model of the blood-brain barrier - can be influenced by interaction with cationic proteins. The various polylysines (Mr ranging from 0.9 to 180 kDa) tested affected the activity of both the Na(+)-dependent ("A") and the Na(+)-independent ("L") systems for neutral amino acid transport. Exposure to the 180 kDa polylysine caused a conspicuous inhibition of both transport systems, associated to an increased passive permeability. There was a constant, Mr-dependent, inhibition of the the L-system-mediated uptake of hydrophobic neutral amino acids. The activity of the A-system was enhanced, upon exposure to polymers larger than 22 kDa reaching its peak at 68 kDa and and declining at higher Mr values. The effect which was Na(+)-ions dependent and abolished by phloretine, could be essentially ascribed to an increased affinity of the MeAIB for its carrier (Km value decreasing from 265 to 169µM in presence of 68 kDa polylysine).