Uptake of vasoactive intestinal peptide by rat liver.

We have investigated the uptake and degradation of vasoactive intestinal peptide (VIP) by rat livers. When liver was perfused with 125I-VIP, less than 20% of the radioactivity was recovered as intact peptide. 125I-VIp bound to specified high-affinity sites on isolated hepatocytes. Half-maximal inhibition of binding occurred at about 1 nM unlabeled VIP. Cell-bound 125I-VIP was degraded to low-molecular-weight products. The percent of 125I-VIP that was bound and degraded was approximately the same at both extremes of the range of VIP concentrations (25-250 pg/ml) reported in portal vein plasma. The lysosomotropic agent chloroquine inhibited 125I-VIP degradation and led to the accumulation of cell-bound 125I-VIP. We conclude that a) most of the VIP secreted from the gastrointestinal tract into portal blood is removed during its passage through the liver, b) VIP binds to specific high-affinity sites on hepatocytes and is probably internalized and degraded by lysosomes, and c) uptake of VIP by liver may serve to prevent the peptide from exerting deleterious systemic effects.