Misbin R I, Wolfe M M, Morris P, Buynitzky S J, McGuigan J E
Am J Physiol. 1982 Aug;243(2):G103-11. doi: 10.1152/ajpgi.1982.243.2.G103.
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.
我们研究了大鼠肝脏对血管活性肠肽（VIP）的摄取和降解。当用125I-VIP灌注肝脏时，回收的放射性中完整肽的含量不到20%。125I-VIP与分离的肝细胞上特定的高亲和力位点结合。未标记的VIP在约1 nM时出现半数最大结合抑制。细胞结合的125I-VIP被降解为低分子量产物。在门静脉血浆中报道的VIP浓度范围（25 - 250 pg/ml）的两个极端情况下，结合并降解的125I-VIP百分比大致相同。溶酶体促渗剂氯喹抑制125I-VIP降解，并导致细胞结合的125I-VIP积累。我们得出以下结论：a）从胃肠道分泌到门静脉血中的大部分VIP在通过肝脏时被清除；b）VIP与肝细胞上特定的高亲和力位点结合，可能被溶酶体内化并降解；c）肝脏对VIP的摄取可能有助于防止该肽产生有害的全身效应。
