DIFFERENT ZONAL DISTRIBUTION OF THE ASIALOGLYCOPROTEIN RECEPTOR, THE ALPHA(2)-MACROGLOBULIN RECEPTOR LOW-DENSITY-LIPOPROTEIN RECEPTOR-RELATED PROTEIN AND THE LIPOPROTEIN-REMNANT RECEPTOR OF RAT-LIVER PARENCHYMAL-CELLS

Periportal and perivenous parenchymal cells were isolated by the digit onin-pulse perfusion method. The digitonin-pulse perfusion was shown t o lead to selective lysis of the correct zone with a straight and shar p border of two to three cells. The mean ratios of alanine aminotransf erase activity (a marker for periportal parenchymal cells) and glutami ne synthetase activity (a perivenous marker) of periportal to periveno us parenchymal cells were 1.76 and 0.025 respectively. Cells were incu bated in vitro with I-125-asialo-orosomucoid (ASOR), I-125-trypsin-act ivated alpha(2)-macroglobulin (alpha(2)M-T) or I-125-beta-migrating ve ry-low-density lipoprotein (beta-VLDL), in order to determine the zona l distribution of the asiaioglycoprotein receptor (ASGPr), the alpha(2 )-macroglobulin receptor/low-density-lipoprotein receptor-related prot ein (alpha(2)Mr/LRP) and the lipoprotein-remnant receptor, respectivel y. Maximum binding capacity for I-125-ASOR on parenchymal cells showed a periportal/perivenous ratio of 0.70. The periportal/perivenous rati o of B-max. values of binding of I-125-alpha(2)M-T to parenchymal cell s was 1.51. The B-max. values of binding of I-125-beta-VLDL, however, were about equal for both cell populations. It is concluded that the m aximum binding capacity of the ASGPr on isolated periportal parenchyma l cells is 0.70 times that of perivenous parenchymal cells. The 1.51-f old higher expression of the alpha(2)Mr/LRP on periportal cells, compa red with perivenous parenchymal cells, indicates a zonal specializatio n for the uptake of the suggested multiple ligands. In contrast, the o bserved homogeneous distribution of the lipoprotein-remnant receptor i s in accordance with the suggestion that lipoprotein remnants bind to a specific receptor, which is different from the alpha(2)Mr/LRP. The z onal heterogeneity in the expression of receptors suggests that recept or-dependent uptake pathways are under zonal control, leading to intra hepatic heterogeneity in the removal of ligands from the blood circula tion.