Asialoorosomucoid hepatobiliary transport is unaltered by the loss of liver asialoglycoprotein receptors in aged rats.
The hepatobiliary transport of asialoorosomucoid (ASOR) was examined in aging male Fischer 344 rats. The time course of transport of 125I-ASOR from blood to bile was identical in both senescent and young adult rats. Peak secretion occurred at approximately 35 minutes after injection via the femoral vein. Total secretion of radiolabeled ASOR (3.6% of injected dose), bile secretion and rate of secretion of radiolabeled ligand (approximately 2% of administered dose/hr/gm bile/liver) were not significantly different for the two age groups. Determination of the binding capacity for 125I-ASOR with liver plasma membrane-enriched preparations showed the membranes from old animals capable of binding approximately 50% less radiolabeled ligand as the young adult animals. Analysis of the distribution of 125I-ASOR autoradiographic grains along the liver lobule indicated extensive uptake of ligand in Zone 2 and 3 cells in senescent animals, whereas uptake in young rats was essentially limited to Zone 1 parenchymal cells. These results indicate that, contrary to the age-related loss of hepatic receptors for dimeric IgA and the concomitant reduction in hepatobiliary secretion of IgA, loss of ASOR binding capacity on liver plasma membranes from old animals is not reflected in diminished hepatobiliary secretion of ASOR. The loss of ASOR binding capacity is offset by the recruitment of Zone 2 and 3 hepatocytes along the liver lobule. This result suggests that hepatic metabolism and hepatobiliary secretion of macromolecules which exhibit a lobular gradient of uptake (e.g. ASOR) will be relatively less affected by loss of receptors compared to ligands which do not display such a gradient (e.g. IgA).
Daniels
C K
CK
Cell Biology & Aging Section, Veterans Administration Medical Center, San Francisco, CA 94121.
Smith
K M
KM
Schmucker
D L
DL
D000375:Aging; D000818:Animals; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D001659:Biliary Tract / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D009961:Orosomucoid / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011971:Receptors, Immunologic / Q000378:metabolism*
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D009961:Orosomucoid; D011971:Receptors, Immunologic; C017030:asialoorosomucoid; D002118:Calcium