Hepatic sequestration and biliary secretion of epidermal growth factor: evidence for a high-capacity uptake system.
Hepatic sequestration and biliary secretion of epidermal growth factor: evidence for a high-capacity uptake system.
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表皮生长因子的肝隔离和胆汁分泌：高容量摄取系统的证据。
DOI：
10.1073/pnas.80.12.3797
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发表时间：
1983
影响因子：
11.1
通讯作者：
Jones,AL
中科院分区：
文献类型：
--
作者：
StHilaire,RJ;Hradek,GT;Jones,AL
表皮生长因子（EGF）促进肝细胞生长，并通过特异性受体结合在肝脏中。我们已经测定了在静脉注射或门静脉内注射125i标记的EGF后，完整大鼠肝脏对EGF的摄取。99%的门静脉内剂量在3分钟内被肝脏吸收，而只有58%的静脉内剂量在10分钟内出现在肝脏。过量未标记的EGF同时处理可抑制摄取。在时间为零时，吸收似乎已经完成。肝脏的消失遵循一级动力学。在门静脉内注射90分钟内，平均19%的注入放射性同位素出现在胆汁中，其中约五分之一的放射性同位素可通过特异性抗egf抗血清免疫沉淀。光显微放射自显像显示一个非常陡峭的门静脉到中央小叶浓度梯度与高容量摄取系统一致。经门静脉内注射或与培养的肝细胞孵育后，标记的EGF显示与其肝受体结合。通过NaDodSO4/聚丙烯酰胺凝胶电泳测定，主受体-配体复合物的Mr约为16万-17万。
Epidermal growth factor (EGF) promotes hepatocyte growth and is bound in the liver by specific receptors. We have determined hepatic uptake of EGF in intact rats after an intravenous or intraportal injection of a bolus of 125I-labeled EGF. Ninety-nine percent of the intraportal dose was taken up by the liver in 3 min, whereas only 58% of the intravenous dose appeared in the liver in 10 min. Uptake was inhibited by simultaneous treatment with an excess of unlabeled EGF. At time zero, uptake appeared to be complete. Disappearance from the liver followed first-order kinetics. Within 90 min of an intraportal injection, an average of 19% of the injected radioisotope appeared in bile, of which approximately one-fifth was shown to be immunoprecipitable with a specific anti-EGF antiserum. Light microscopic autoradiography demonstrated a very steep portal-to-central lobular concentration gradient consistent with a high-capacity uptake system. After intraportal injection or after incubation with cultured hepatocytes, labeled EGF was shown to be bound to its hepatic receptors. The main receptor-ligand complex had a Mr of approximately equal to 160,000-170,000, determined by NaDodSO4/polyacrylamide gel electrophoresis.