Prothrombin plasma clearance is not mediated by hepatic asialoglycoprotein receptors

The hepatic asialoglycoprotein receptor (AGPR) system can efficiently internalize and degrade circulating glycoproteins which lack terminal sialic acids on their carbohydrate chains. Since pro-thrombin is a glycosylated plasma protein, possible involvement of AGPR system in its clearance from circulation was evaluated. The half lives of bovine 125I-prothrombin and 125I-asialoprothrombin, injected intravenously into rats, were 192 and 1.8 minutes, respectively. Asialoprothrombin appeared to be cleared by the hepatic AGPRs since 33% of it accumulated in the liver at 30 minutes and its clearance was competitively blocked by simultaneous administration of increasing amounts of asialofetuin. Only 5% of prothrombin accumulated in the liver at 3 hours and injections asialofetuin in amounts capable of saturating the AGPR for the duration of four asialoprothrombin half lives had no effect on the disappearance of prothrombin. Our observations indicate that, although asialoprothrombin is readily cleared from plasma by the AGPR system, prothrombin is not. Thus these receptors do not appear to be involved in physiological processes that control prothrombin half life.