Processing of cholecystokinin by isolated liver cells.
Processing of cholecystokinin by isolated liver cells.
复制标题
分离的肝细胞处理胆囊收缩素。
DOI：
10.1152/ajpgi.1989.257.2.g242
复制
发表时间：
1989
期刊：
影响因子：
--
通讯作者：
LaRusso,NF
中科院分区：
文献类型：
--
作者：
Gores,GJ;Kost,LJ;Miller,LJ;LaRusso,NF
虽然胆囊收缩素（CCK）的肝脏摄取已被证实，但涉及的肝细胞和摄取机制仍不清楚。我们使用分散的大鼠肝细胞、库普弗细胞和肝内皮细胞来表征放射性标记的CCK肽的摄取和代谢。只有大鼠肝细胞显示125i标记的胆囊收缩素八肽（125I-CCK-8）的显著摄取。肝细胞摄取肽的特异性与离体灌注大鼠肝脏相似，提取125I-CCK-8比提取125I-CCK-33高7倍。摄取是饱和的，因为10(-4)M CCK-4抑制了85%的125I-CCK-8的摄取。摄取是快速的、温度依赖的、广泛的，并被代谢抑制、一种蛋白水解酶（胰蛋白酶）、有机阴离子（硫代溴代眼蛋白和牛磺胆酸）和一种阴离子转运抑制剂4,4'-二异硫氰二苯乙烯-2,2'-二磺酸所降低。此外，摄取依赖于细胞外阴离子，而不依赖于细胞外钠、钙或镁。摄取后，肝细胞以时间和温度依赖的方式释放放射性标签，主要以代谢形式释放。因此，肝细胞是通过一个活跃的阴离子依赖过程提取CCK的肝细胞。摄取过程的特征类似于描述的有机阴离子和小的环状肽，并表明小的线性肽可能通过类似的机制进行肝细胞提取。
Although hepatic uptake of cholecystokinin (CCK) has been demonstrated, the liver cell involved and the mechanism of uptake remain unclear. We have used dispersed rat hepatocytes, Kupffer cells, and hepatic endothelial cells to characterize uptake and metabolism of radiolabeled CCK peptides. Only rat hepatocytes showed significant uptake of 125I-labeled cholecystokinin octapeptide (125I-CCK-8). Peptide specificity of uptake by hepatocytes was similar to that seen in the isolated perfused rat liver, with extraction of 125I-CCK-8 being sevenfold greater than that of 125I-CCK-33. Uptake was saturable, as 10(-4) M CCK-4 inhibited uptake of 125I-CCK-8 by 85%. Uptake was rapid, temperature dependent, and extensive and was decreased by metabolic inhibition, a proteolytic enzyme (trypsin), organic anions (sulfobromophthalein and taurocholic acid), and an inhibitor of anion transport 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. In addition, uptake was dependent on extracellular anions but not on extracellular sodium, calcium, or magnesium. After uptake, hepatocytes released radiolabel in a time- and temperature-dependent manner, predominantly in metabolized forms. Thus the hepatocyte is the liver cell that extracts CCK by an active, anion-dependent process. The characteristics of the uptake process resemble those described for organic anions and small, cyclic peptides and suggest that small, linear peptides may undergo hepatocyte extraction by a similar mechanism.