抗肿瘤药物5-（3,3-二甲基-1-三氮烯基）咪唑-4-甲酰胺（DTIC）可抑制大鼠肝脏中的环磷酸腺苷磷酸二酯酶，并增强激素对肝细胞和肝癌细胞的作用。
The antitumour agent 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide (DTIC) inhibits rat liver cAMP phosphodiesterase and amplifies hormone effects in hepatocytes and hepatoma cells.
作者信息
Larsson P G, Haffner F, Brłnstad G O, Christoffersen T
出版信息
Br J Cancer. 1979 Nov;40(5):768-73. doi: 10.1038/bjc.1979.259.
Abstract
The antitumour agent 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) was found to inhibit competitively the low-Km cyclic AMP phosphodiesterase activity in an ammonium-sulphate-precipitable fraction of the 2,000g supernatant of rat liver. With substrate concentration at 0.25 microM, I50 was 790 microM for DTIC and 350 microM for theophylline. DTIC at 2 mM more than doubled the cAMP response to glucagon in hepatocytes and to adrenaline in MH1C1 hepatoma cells, indicating that it also exerts its inhibitory effect on the phosphodiesterase in intact cells. The possible contribution of the phosphodiesterase inhibition to the growth-inhibitory and cytotoxic effects of DTIC is discussed.
摘要
抗肿瘤药物5-(3,3-二甲基-1-三氮烯)咪唑-4-甲酰胺（DTIC）被发现可竞争性抑制大鼠肝脏2000g上清液硫酸铵沉淀部分中的低Km环磷酸腺苷磷酸二酯酶活性。底物浓度为0.25微摩尔时，DTIC的半数抑制浓度（I50）为790微摩尔，茶碱的I50为350微摩尔。2毫摩尔的DTIC使肝细胞中对胰高血糖素以及MH1C1肝癌细胞中对肾上腺素的环磷酸腺苷反应增加了一倍多，这表明它对完整细胞中的磷酸二酯酶也有抑制作用。本文讨论了磷酸二酯酶抑制作用对DTIC的生长抑制和细胞毒性作用可能的贡献。
相似文献
1
The antitumour agent 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide (DTIC) inhibits rat liver cAMP phosphodiesterase and amplifies hormone effects in hepatocytes and hepatoma cells.抗肿瘤药物5-（3,3-二甲基-1-三氮烯基）咪唑-4-甲酰胺（DTIC）可抑制大鼠肝脏中的环磷酸腺苷磷酸二酯酶，并增强激素对肝细胞和肝癌细胞的作用。
Br J Cancer. 1979 Nov;40(5):768-73. doi: 10.1038/bjc.1979.259.
2
Effect of the antitumour agent 5-(3,3-dimethyl-1-triazeno imidazole-4-carboxamide (DTIC) on cyclic AMP levels in intact MH1C1 hepatoma cells.抗肿瘤药物5-（3,3-二甲基-1-三氮烯基咪唑-4-甲酰胺）（DTIC）对完整的MH1C1肝癌细胞中环磷酸腺苷水平的影响。
Acta Pharmacol Toxicol (Copenh). 1980 Aug;47(2):93-7. doi: 10.1111/j.1600-0773.1980.tb01846.x.
3
4
The phorbol ester TPA inhibits cyclic AMP phosphodiesterase activity in intact hepatocytes.佛波酯TPA可抑制完整肝细胞中环磷酸腺苷磷酸二酯酶的活性。
FEBS Lett. 1986 Nov 24;208(2):455-9. doi: 10.1016/0014-5793(86)81068-7.
5
Inhibitory effect of prostaglandins on the stimulation by glucagon and adrenaline of formation of cyclic AMP in rat hepatocytes.前列腺素对胰高血糖素和肾上腺素刺激大鼠肝细胞中环磷酸腺苷形成的抑制作用。
Eur J Biochem. 1981 Jul;117(2):369-74. doi: 10.1111/j.1432-1033.1981.tb06347.x.
6
Effects of 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide [NSC 45388, DTIC] on neuroblastoma cells in culture.5-（3,3-二甲基-1-三氮烯基）咪唑-4-甲酰胺[NSC 45388，达卡巴嗪]对培养的神经母细胞瘤细胞的作用。
Biochem Biophys Res Commun. 1977 Jun 6;76(3):778-83. doi: 10.1016/0006-291x(77)91568-6.
7
The phosphodiesterase 3 inhibitor cilostamide enhances inotropic responses to glucagon but not to dobutamine in rat ventricular myocardium.磷酸二酯酶3抑制剂西洛酰胺可增强大鼠心室肌对胰高血糖素的变力反应，但对多巴酚丁胺无此作用。
Eur J Pharmacol. 2005 Apr 11;512(2-3):207-13. doi: 10.1016/j.ejphar.2005.01.056.
8
Responsiveness to glucagon by isolated rat hepatocytes controlled by the redox state of the cytosolic nicotinamide--adenine dinucleotide couple acting on adenosine 3':5'-cyclic monophosphate phosphodiesterase.分离的大鼠肝细胞对胰高血糖素的反应性受作用于腺苷3':5'-环磷酸单酯磷酸二酯酶的胞质烟酰胺-腺嘌呤二核苷酸偶联的氧化还原状态控制。
Biochem J. 1978 Dec 15;176(3):805-16. doi: 10.1042/bj1760805.
9
Inhibition of adenosine 3',5'-monophosphate phosphodiesterase by nicotinamide and its homologues in vitro.烟酰胺及其同系物在体外对3',5'-环磷酸腺苷磷酸二酯酶的抑制作用。
Physiol Chem Phys. 1975;7(2):125-32.
10
[Study of the role of endogenous 3',5'-cyclic AMP in the radioresistance of the cell].
Vopr Med Khim. 1976 Jul-Aug;22(4):533-8.
本文引用的文献
1
Pharmacologic studies of the antitumor agent 5-(dimethyltriazeno)imidazole-4-carboxamide.抗肿瘤药物5-（二甲基三氮烯）咪唑-4-甲酰胺的药理学研究。
Cancer Res. 1968 Dec;28(12):2448-53.
2
3
Induction of tryptophan oxygenase in primary rat liver cell suspensions by glucocorticoid hormone.
Exp Cell Res. 1972 Jun;72(2):571-4. doi: 10.1016/0014-4827(72)90034-1.
4
4 (or 5)-diazoimidazole-5 (or 4)-carboxamide and related triazenoimidazoles as antibacterial agents: their effects on nucleic acid metabolism of Escherichia coli B.4（或5）-重氮咪唑-5（或4）-甲酰胺及相关三氮烯咪唑类作为抗菌剂：它们对大肠杆菌B核酸代谢的影响
Biochem Pharmacol. 1969 Jun;18(6):1463-72. doi: 10.1016/0006-2952(69)90260-3.
5
6
Mechanism of action of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide in mammalian cells in culture.5-（3,3-二甲基-1-三氮烯基）咪唑-4-甲酰胺在培养的哺乳动物细胞中的作用机制
Biochem Pharmacol. 1972 Sep 1;21(17):2335-43. doi: 10.1016/0006-2952(72)90384-x.
7
The reaction of alkylating agents with cyclic 3',5'-nucleotide phosphodiesterase.
Chem Biol Interact. 1974 Aug;9(2):145-53. doi: 10.1016/0009-2797(74)90006-4.
8
Development of cyclic AMP metabolism in rat liver. A correlative study of tissue levels of cyclic AMP, accumulation of cyclic AMP in slices, adenylate cyclase activity and cyclic nucleotide phosphodiesterase activity.大鼠肝脏中环磷酸腺苷代谢的发展。环磷酸腺苷组织水平、切片中环磷酸腺苷积累、腺苷酸环化酶活性和环核苷酸磷酸二酯酶活性的相关性研究。
Biochim Biophys Acta. 1973 Jul 28;313(2):338-49. doi: 10.1016/0304-4165(73)90033-0.
9
Preparation of rat liver cells. I. Effect of Ca 2+ on enzymatic dispersion of isolated, perfused liver.大鼠肝细胞的制备。I. Ca²⁺ 对离体灌注肝脏酶分散作用的影响。
Exp Cell Res. 1972 Oct;74(2):450-4. doi: 10.1016/0014-4827(72)90400-4.
10
Radioimmunoassay for the measurement of adenosine 3',5'-cyclic phosphate.用于测量3',5'-环磷酸腺苷的放射免疫测定法。
Proc Natl Acad Sci U S A. 1969 Sep;64(1):367-73. doi: 10.1073/pnas.64.1.367.
Zotero 插件