Impairment of glucagon-induced hepatic system A activity by short-term ethanol administration in the rat.
Impairment of glucagon-induced hepatic system A activity by short-term ethanol administration in the rat.
复制标题
大鼠短期乙醇给药对胰高血糖素诱导的肝系统 A 活性的损害。
DOI：
10.1016/0016-5085(94)90608-4
复制
发表时间：
1994
期刊：
影响因子：
29.4
通讯作者：
Banks,RK
中科院分区：
文献类型：
--
作者：
Mailliard,ME;Cariappa,R;Banks,RK
背景/目标：系统 A 是一种膜结合、激素调节的氨基酸载体，由肝再生诱导并受到乙醇损害。乙醇抑制A系统的机制尚不清楚；本研究探讨了乙醇对激素诱导后系统 A 活性的亚细胞表达的影响。方法：对大鼠进行激素治疗和短期乙醇给药后，分离肝脏高尔基体和质膜囊泡，检测系统 A 转运，并测定动力学参数。结果：乙醇给药后 4 小时，系统 A 活性的初始速率降低 30% ± 9% 和 19% ± 7% 进入高尔基体和质膜分别为囊泡。无论其亚细胞来源如何，对照囊泡和乙醇处理的囊泡的 2-(甲基氨基)-异丁酸摄取亲和常数没有变化。然而，高尔基体囊泡中 A 系统转运的最大速度从 1030 pmol·mg−1 Protein ·10 s−1 下降到 850 pmol·mg−1 Protein ·10 s−1，质膜囊泡中从 740 pmol·mg−1 Protein 10 s−1 下降到 355 pmol·mg−1 Protein 10 s−1。 结论：乙醇会损害高尔基体和质膜囊泡中激素诱导的 A 系统活性。乙醇可能通过损害载体生物合成或表达来降低胰高血糖素对系统 A 活性的诱导。
Background/Aims:System A is a membrane-bound, hormonally regulated carrier of amino acids that is induced by liver regeneration and impaired by ethanol. The mechanism of ethanol inhibition of system A is unknown; this study examines the effects of ethanol on the subcellular expression of system A activity following hormonal induction.Methods:Following hormonal treatment and short-term ethanol administration to rats, isolated liver Golgi and plasma membrane vesicles were examined for system A transport, and the kinetic parameters were determined.Results:Four hours after ethanol administration, the initial rate of system A activity was depressed 30% ± 9% and 19% ± 7% into Golgi and plasma membrane vesicles, respectively. The affinity constant of 2-(methylamino)-isobutyric acid uptake was unchanged between control and ethanol-treated vesicles, regardless of their subcellular origin. However, the maximal velocity of system A transport decreased from 1030 to 850 pmol ·mg−1protein ·10 s−1in Golgi vesicles and from 740 to 355 pmol ·mg−1protein 10 s−1in plasma membrane vesicles.Conclusions:Ethanol impairs hormonally induced system A activity in Golgi as well as in the plasma membrane vesicles. Ethanol potentially reduces glucagon induction of system A activity through an impairment of carrier biosynthesis or expression.