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[环磷酸腺苷、胰高血糖素和胰岛素对大鼠肝脏和胰腺中胍乙酸-N-甲基转移酶活性的刺激作用]

[The stimulating effect of cyclic AMP, glucagon and insulin on guanidine acetate-N-methyltransferase activity in rat liver and pancreas].

作者信息

Karelin A A, Mardashev S R

出版信息

Biokhimiia. 1976 Feb;41(2):316-23.

PMID:179611
Abstract

N6,O2'-dibutyrylcyclo-3',5'-AMP injected to intact rats alone or in combination with theophylline increases the activity of guanidine acetate methyltransferase (GAMT) in liver and pancreas. Cyclic 3',5'-AMP and its dibutyryl analog administered immediately or two hours after the suturing of common bile duct (SCBD) stimulate the increase of pancreatic GAMT activity 2-3 fold. Glucagon, injected intraabdominally simultaneously with SCBD and administration of theophylline, dramatically increases the theophylline effect on the GAMT activity. The freezing of rat pancreas pretreated witn secretin, a hormone structurally similar to glucagon, results in a 1.5-2-fold increase of creatine synthesis from S-adenosylmethionine and guanidinacetic acid. An hour after glucagon administration to intact rats the GAMT activity of liver increases 9 times. The effect of glucagon is enhanced by insulin. Cycloheximide inhibits the increase of GAMT activity, induced by glucagon or a combination of glucagon and insulin. Experiments on tissue homogenates demonstrate that 3',5'-AMP in concentrations of 10(-8) --10(-2) M does not affect the GAMT activity or to some extent inhibits the enzyme. The homogenate incubation in a medium containing 10(-5) M epinephrine or 10(-7) M caffeine and 5 mM Mg2+ leads to an increase in the GAMT activity. Oligomycin removes the stimulating effects of caffeine and Mg2+ on the enzyme activation. This is probably due to the presence of 3',5'-AMP-dependent protein kinase in the mechanism of GAMT activation by cyclic AMP.

摘要

单独或与茶碱联合注射到完整大鼠体内的N6,O2'-二丁酰环-3',5'-AMP可增加肝脏和胰腺中胍乙酸甲基转移酶(GAMT)的活性。在胆总管缝合(SCBD)后立即或两小时给予环3',5'-AMP及其二丁酰类似物,可刺激胰腺GAMT活性增加2-3倍。与SCBD同时腹腔注射胰高血糖素并给予茶碱,可显著增强茶碱对GAMT活性的作用。用促胰液素(一种结构与胰高血糖素相似的激素)预处理大鼠胰腺后进行冷冻,可使由S-腺苷甲硫氨酸和胍基乙酸合成肌酸的量增加1.5-2倍。给完整大鼠注射胰高血糖素一小时后肝脏的GAMT活性增加9倍。胰岛素可增强胰高血糖素的作用。放线菌酮抑制由胰高血糖素或胰高血糖素与胰岛素联合诱导的GAMT活性增加。对组织匀浆的实验表明,浓度为10(-8)--10(-2)M的3',5'-AMP不影响GAMT活性或在一定程度上抑制该酶。在含有10(-5)M肾上腺素或10(-7)M咖啡因和5mM Mg2+的培养基中孵育匀浆会导致GAMT活性增加。寡霉素消除咖啡因和Mg2+对酶激活的刺激作用。这可能是由于在环AMP激活GAMT的机制中存在3',5'-AMP依赖性蛋白激酶。

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