Hepatic uptake of asialoglycoprotein is different among mammalian species due to different receptor distribution

Abstract

Isolated hepatocytes of rat, rabbit and guinea pig were found to take up and degrade 125I-labelled asialoorosomucoid at different rates with the rank order: rabbit > rat > guinea pig. Measurement of 125I-asialoorosomucoid binding at 4°C to these hepatocytes revealed that all these cells had two classes of receptors with a major difference occurring in the number of high-affinity binding sites. The average binding affinity constants ( K) and receptor concentration ( N) calculated from a least-square analysis of the Scatchard plots were K 1 = 1.5·10 9 M −1, K 2=0.93·10 7 M −7, N 1 = 0.049 pmol/mg cell protein and N 2 = 0.27 pmol/mg cell protein for the rat; K 2 = 3.16·10 7 M −1, N 1 = 0.027 pmol/mg cell protein and N 2 = 0.13 pmol/mg cell protein for the guinea pig and K 1 = 0.74·10 9 M −1, K 2 = 3.85·10 7 M −1, N 1 = 0.205 pmol/mg cell protein and N 2 = 0.37 pmol/mg cell protein or the rabbit hepatocytes, respectively. Measurement of the total number of cellular receptors after solubilizatio with Triton X-100 also revealed the same receptor concentration rank order of rabbit (5.8 pmol/mg cell protein) > rat (0.55 pmol/mg cell protein) > guinea pig (0.18 pmol/mg cell protein). Intravenous injection of 125I-asialoorosomucoid into anesthetized animals of matched body weight also indicated that the rate of plasma clearance and the rate of appearance of the degraded product of the tracer were different among these species with the same rank order as the observed with isolated hepatocytes. Thus there is a fundamental difference in the number of asialoglycoprotein receptors both on the cell surface and inside hepatocytes of these mammalian species.