血管加压素、肾上腺素和血管紧张素II对肝细胞中肌醇三磷酸形成的刺激及其与胞质游离Ca2+变化的关系。

Stimulation of inositol trisphosphate formation in hepatocytes by vasopressin, adrenaline and angiotensin II and its relationship to changes in cytosolic free Ca2+.

作者信息

Charest R, Prpić V, Exton J H, Blackmore P F

出版信息

Biochem J. 1985 Apr 1;227(1):79-90. doi: 10.1042/bj2270079.

DOI:10.1042/bj2270079

PMID:3873238

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1144811/

Abstract

At maximally effective concentrations, vasopressin (10(-7) M) increased myo-inositol trisphosphate (IP3) in isolated rat hepatocytes by 100% at 3 s and 150% at 6 s, while adrenaline (epinephrine) (10(-5) M) produced a 17% increase at 3 s and a 30% increase at 6 s. These increases were maintained for at least 10 min. Both agents increased cytosolic free Ca2+ [( Ca2+]i) maximally by 5 s. Increases in IP3 were also observed with angiotensin II and ATP, but not with glucagon or platelet-activating factor. The dose-responses of vasopressin and adrenaline on phosphorylase and [Ca2+]i showed a close correspondence, whereas IP3 accumulation was 20-30-fold less sensitive. However, significant (20%) increases in IP3 could be observed with 10(-9) M-vasopressin and 10(-7) M-adrenaline, which induce near-maximal phosphorylase activation. Vasopressin-induced accumulation of IP3 was potentiated by 10mM-Li+, after a lag of approx. 1 min. However the rise in [Ca2+]i and phosphorylase activation were not potentiated at any time examined. Similar data were obtained with adrenaline as agonist. Lowering the extracellular Ca2+ to 30 microM or 250 microM did not affect the initial rise in [Ca2+]i with vasopressin but resulted in a rapid decline in [Ca2+]i. Brief chelation of extracellular Ca2+ for times up to 4 min also did not impair the rate or magnitude of the increase in [Ca2+]i or phosphorylase a induced by vasopressin. The following conclusions are drawn from these studies. IP3 is increased in rat hepatocytes by vasopressin, adrenaline, angiotensin II and ATP. The temporal relationships of its accumulation to the increases in [Ca2+]i and phosphorylase a are consistent with it playing a second message role. Influx of extracellular Ca2+ is not required for the initial rise in [Ca2+]i induced by these agonists, but is required for the maintenance of the elevated [Ca2+]i.

摘要

在最大有效浓度下，血管加压素（10⁻⁷M）使离体大鼠肝细胞中的肌醇三磷酸（IP₃）在3秒时增加100%，在6秒时增加150%，而肾上腺素（10⁻⁵M）在3秒时增加17%，在6秒时增加30%。这些增加至少维持10分钟。两种药物均在5秒时使胞质游离Ca²⁺（[Ca²⁺]i）达到最大增加。血管紧张素II和ATP也能使IP₃增加，但胰高血糖素或血小板活化因子则不能。血管加压素和肾上腺素对磷酸化酶和[Ca²⁺]i的剂量反应显示出密切的对应关系，而IP₃积累的敏感性则低20 - 30倍。然而，10⁻⁹M血管加压素和10⁻⁷M肾上腺素可使IP₃显著（20%）增加，这两种浓度可诱导磷酸化酶接近最大程度的活化。血管加压素诱导的IP₃积累在约1分钟的延迟后被10mM - Li⁺增强。然而，在任何检测时间，[Ca²⁺]i的升高和磷酸化酶的活化均未被增强。以肾上腺素作为激动剂也获得了类似的数据。将细胞外Ca²⁺浓度降至30μM或250μM并不影响血管加压素引起的[Ca²⁺]i的初始升高，但导致[Ca²⁺]i迅速下降。对细胞外Ca²⁺进行长达4分钟的短暂螯合也不会损害血管加压素诱导的[Ca²⁺]i或磷酸化酶a增加的速率或幅度。从这些研究中得出以下结论。血管加压素、肾上腺素、血管紧张素II和ATP可使大鼠肝细胞中的IP₃增加。其积累与[Ca²⁺]i和磷酸化酶a增加的时间关系与其作为第二信使的作用一致。这些激动剂诱导的[Ca²⁺]i的初始升高不需要细胞外Ca²⁺的内流，但维持升高的[Ca²⁺]i则需要细胞外Ca²⁺的内流。