title: Modulation of the transport of bilirubin and asialoorosomucoid during liver regeneration.
abstract: The normal rat hepatocyte divides approximately once per year but, following two thirds hepatectomy, rapid cellular replication occurs throughout the remaining liver remnant. Using a multiple indicator dilution technique, single-pass transport of 3H-bilirubin and 125I-asialoorosomucoid was studied in isolated perfused liver from 6 hr to 6 d after two thirds hepatectomy or sham surgery. Influx (k1), efflux (k2), and sequestration (k3) rates were quantitated by computer analysis. k1 for 3H-bilirubin fell by over 50% within 6 hr after two thirds hepatectomy and returned to normal 4 d later. k2 progressively decreased with a nadir at 2 d, and returned to normal by 4 d. k3 was transiently depressed, and became normal within 2 d. Although hepatic uptake of asialoglycoproteins has been thought to be irreversible, the experimental data required k2 and k3 parameters for best fit. Similar to results for 3H-bilirubin, the k1 of 125I-asialoorosomucoid was 20% of normal at 1 d after two thirds hepatectomy, and returned to normal by 6 d. Unlike results for 3H-bilirubin, there was a prolonged 50% reduction of k2 and k3 with return to normal by 6 d. The transport changes during regeneration are independent of reduced liver mass or changes in hepatic spaces of distribution. The fact that influx of both compounds reaches a nadir at the time of greatest cellular proliferation with subsequent return to normal suggests a "maturation" of liver cell function for restoration of these specific hepatocyte functions. Modulation of the hepatocyte receptor for desialylated glycoproteins may also be required for cellular recognition as a prerequisite for proliferative responses.
mesh_terms: D000818:Animals; D001212:Asialoglycoproteins; D001663:Bilirubin / Q000378:metabolism*; D006498:Hepatectomy; D007201:Indicator Dilution Techniques; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism*; D008115:Liver Regeneration; D008297:Male; D009929:Organ Size; D009961:Orosomucoid / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D001212:Asialoglycoproteins; D009961:Orosomucoid; C017030:asialoorosomucoid; D001663:Bilirubin