Phwmacology.University of Beme, Switzerland EGFis taken up by the liver through receptor-mediated en& cy tosis; most is degraded but a small percentage is secreted intact into bile. Intracellular processing is thought to be important in
signal transduction. Both, transcytosis and the lysosomal pathway utilize vesicular trnnspon. In this study we investigated the D20 effect on the
heptic handling of ECF. Heavy water intluences the
cytoskeleton (F-actin) of leukocytes. In liver. we have recently shown it to induce cholestasis. and to inhibitc transcytosis of horseradish peroxidase. Livers from male SD rats were perfused in situ in a recirculating system with Krebs-Ringer-bicsrbonate buffer containing 2% BSA. made up in either 100% H@ or 60% D@: bile salt secretion was maintained by 3 taurocholate infusion of 2Bmol/mitVkg. After portal bolus injection of tW-EGF. 10 min bile samples were collected for 60 min. EGF extraction was slightly reduced and averaged 79.lf1.2% (*SD) and 74.4+1.5% in the H20 and the D20 perfused liver, respectively (peO.01). Remaining radioactivity in the liver after 69 mitt increased from 42.7*1.7% to Sl.Sf1.9%. Total radioactivity released into the perfusate arera_eed 35.5fl.SQ and 21.lf2.496 (pcO.001) and did not contain mtact EGF. Total b&try output of radioactivity and intact EGF were reduced (3.WO.S% vs 1.4f 0.6% and 0.5~~39% vs. 0.17?0.05%; p
SlOl