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.
D000818:Animals; D002738:Chloroquine / Q000494:pharmacology; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007457:Iodine Radioisotopes; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D005768:Gastrointestinal Hormones; D007328:Insulin; D007457:Iodine Radioisotopes; D014660:Vasoactive Intestinal Peptide; D002738:Chloroquine