Surface receptors for pancreatic hormones in dog and rat hepatocytes: qualitative and quantitative differences in hormone-target cell interactions.

Surface receptors for pancreatic hormones in dog and rat hepatocytes: qualitative and quantitative differences in hormone-target cell interactions.
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狗和大鼠肝细胞中胰腺激素的表面受体:激素-靶细胞相互作用的定性和定量差异。

DOI:
10.1073/pnas.79.7.2167
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发表时间:
1982
影响因子:
11.1
通讯作者:
Tager,HS
Tager,HS
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bonnevie-Nielsen,V;Polonsky,KS;Jaspan,JJ;Rubenstein,AH;Schwartz,TW;Tager,HS

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为了评估不同物种肝细胞中肽受体相互作用动力学的潜在差异,我们开发了一种简单的犬肝细胞分离程序。细胞(通过胶原酶灌注摘除的狗肝叶获得)以均匀的高活力和产量分离。此外,分离的犬肝细胞可耐受在限定培养基中孵育至少4小时,仅存活率轻微降低,[125 I]碘胰岛素或[125 I]碘胰高血糖素与细胞表面受体结合的动力学无变化。肽类激素与离体犬和大鼠肝细胞相互作用的比较表明:(i)在30 ℃和37 ℃下,大鼠和犬肝细胞中[125 I]碘胰高血糖素与特异性膜受体的结合速度均快于[125 I]碘胰岛素;(ii)在狗肝细胞中,[125 I]碘胰高血糖素在30 ℃时的稳态结合大于[125 I]碘胰岛素,但在大鼠肝细胞中保持相反的关系;(iii)未标记激素的存在增强了[125 I]碘胰岛素从两种动物肝细胞的解离速率,而受体结合的[125 I]碘胰高血糖素的解离速率仅在犬肝细胞中因未标记胰高血糖素的存在而增强;和(iv)[125 I]碘胰腺多肽既不与大鼠肝细胞结合,也不与狗肝细胞结合,尽管[125 I]碘酪酰化肽以异常高的表观解离常数与大鼠肝细胞结合。在确认胰腺激素与分离肝细胞结合的基本发现的同时,这种比较表明,胰腺-靶细胞相互作用的定性和定量方面都可以显示出种间变异性。
In order to evaluate potential differences in the kinetics of peptide hormone-receptor interactions in hepatocytes of different species, we developed a simple procedure for the isolation of canine hepatocytes. Cells (obtained by collagenase perfusion of an extirpated dog liver lobe) were isolated with uniform high viability and yield. In addition, isolated dog hepatocytes tolerated incubation for at least 4 hr in defined medium with only a slight decrease in viability and with no change in the kinetics of [125I]iodoinsulin or [125I]iodoglucagon binding to cell-surface receptors. Comparisons of peptide hormone interactions with isolated dog and rat hepatocytes showed that (i) [125I]iodoglucagon associated with specific membrane receptors more rapidly than did [125I]iodoinsulin, for both rat and dog hepatocytes and at both 30 degrees C and 37 degrees C; (ii) the steady-state binding of [125I]iodoglucagon at 30 degrees C was greater than that of [125I]iodoinsulin in dog hepatocytes, but the reverse relationship held in rat hepatocytes; (iii) the rate of dissociation of [125I]iodoinsulin from hepatocytes of both species was enhanced by the presence of the unlabeled hormone, whereas the rate of dissociation of receptor-bound [125I]iodoglucagon was enhanced by the presence of unlabeled glucagon only in hepatocytes derived from the dog; and (iv) [125I]iodopancreatic polypeptide bound to neither rat nor dog hepatocytes, although the [125I]iodotyrosylated peptide bound to rat hepatocytes with an unusually high apparent dissociation constant. While confirming essential findings of pancreatic hormone binding to isolated hepatocytes, this comparison suggests that both qualitative and quantitative aspects of hormone-target cell interactions can show interspecies variability.