PROTAMINE-MEDIATED TRANSPORT OF ALBUMIN INTO BRAIN AND OTHER ORGANS OF THE RAT - BINDING AND ENDOCYTOSIS OF PROTAMINE-ALBUMIN COMPLEX BY MICROVASCULAR ENDOTHELIUM

High doses of intravenous protamine cause generalized vascular permeab ility changes in brain and other organs, and concomitant hypoproteinem ia. The present investigations test the hypothesis that protamine has a dual action of both binding serum proteins and of undergoing absorpt ive-mediated transcytosis through microvascular endothelial barriers. Binding of albumin to protamine was demonstrated using equilibrium dia lysis, and protamine was shown to selectively augment the uptake of al bumin, but not sucrose, in isolated bovine or human brain capillaries. In contrast, the anionic macromolecule, dextran sulfate, resulted in an increased capillary uptake of both albumin and sucrose in vitro. Th e selective effects of protamine on albumin transport were also docume nted in vivo using an external organ technique; the intravenous inject ion of 1.5 mg/kg protamine resulted in a marked and selective influx o f albumin into brain, heart, kidney, lung, and liver, and the increase d albumin transport exceeded the increased sucrose uptake in some orga ns by an order of magnitude. The transcytosis of protamine through the cerebral microvascular barrier was documented with an internal caroti d artery perfusion technique. In summary, these studies provide eviden ce for protamine-mediated vectorial transport of albumin through micro vascular barriers in brain and other organs.