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福司可林对大鼠脑和睾丸中腺苷酸环化酶的激活作用。

Activation of adenylate cyclase by forskolin in rat brain and testis.

作者信息

Sano M, Kitajima S, Mizutani A

出版信息

Arch Biochem Biophys. 1983 Feb 1;220(2):333-9. doi: 10.1016/0003-9861(83)90421-6.

DOI:10.1016/0003-9861(83)90421-6
PMID:6681696
Abstract

Detergent-dispersed adenylate cyclase from rat cerebrum was detected in two components, one sensitive to Ca2+ and calmodulin and another sensitive to fluoride or guanyl-5'-yl imidodiphosphate (Gpp(NH)p). The enzyme activity of both components was markedly augmented by forskolin assayed in the presence or absence of other enzyme activators (e.g., NaF, Gpp(NH)p, calmodulin). The catalytic subunit fraction in which G/F protein was totally lacking was also activated by forskolin. During 1-35 days of postnatal development, the basal adenylate cyclase activities in either cerebrum and cerebellum particulate preparations progressively increased. While the fluoride sensitivity of the cerebrum and cerebellum enzyme increased during postnatal development, the responsiveness to forskolin remained unaltered. There was no enhancement of soluble adenylate cyclase (from rat testis) by forskolin under the assay conditions in which there was a marked stimulatory action on the particulate enzyme. The results seen with the solubilized enzyme, with either Lubrol PX or cholate, indicate that the effects of forskolin on the cyclase do not require either G/F protein or calmodulin and the results of our study of brain enzymes support this view. Data on soluble testis cyclase (a poor or absent response to forskolin by this enzyme) imply that it lacks a protein (other than the catalytic unit) which could confer greater stimulation. The present results do not rule out an alternative explanation that forskolin stimulates adenylate cyclase by a direct interaction with the catalytic subunit, if the catalytic proteins do differ widely in various species of cells and their response to this diterpene.

摘要

大鼠大脑中经去污剂分散的腺苷酸环化酶可分为两个组分,一个对Ca2+和钙调蛋白敏感,另一个对氟化物或鸟苷-5'-亚基亚氨二磷酸(Gpp(NH)p)敏感。在有或没有其他酶激活剂(如NaF、Gpp(NH)p、钙调蛋白)存在的情况下进行检测,两种组分的酶活性均被福斯可林显著增强。完全缺乏G/F蛋白的催化亚基部分也被福斯可林激活。在出生后1至35天的发育过程中,大脑和小脑颗粒制剂中的基础腺苷酸环化酶活性逐渐增加。虽然大脑和小脑酶对氟化物的敏感性在出生后发育过程中增加,但对福斯可林的反应性保持不变。在对颗粒酶有显著刺激作用的检测条件下,福斯可林对可溶性腺苷酸环化酶(来自大鼠睾丸)没有增强作用。用Lubrol PX或胆酸盐溶解酶所得到的结果表明,福斯可林对环化酶的作用不需要G/F蛋白或钙调蛋白,我们对脑酶的研究结果支持这一观点。关于可溶性睾丸环化酶的数据(该酶对福斯可林反应不佳或无反应)表明,它缺乏一种能带来更大刺激作用的蛋白质(催化亚基除外)。如果催化蛋白在不同种类的细胞中确实存在很大差异以及它们对这种二萜的反应不同,那么目前的结果并不排除另一种解释,即福斯可林通过与催化亚基直接相互作用来刺激腺苷酸环化酶。

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Activation of adenylate cyclase by forskolin in rat brain and testis.福司可林对大鼠脑和睾丸中腺苷酸环化酶的激活作用。
Arch Biochem Biophys. 1983 Feb 1;220(2):333-9. doi: 10.1016/0003-9861(83)90421-6.
2
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Forskolin: unique diterpene activator of adenylate cyclase in membranes and in intact cells.福斯高林:膜及完整细胞中独特的腺苷酸环化酶二萜激活剂。
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Forskolin-induced change of the size of adenylate cyclase.福司可林诱导的腺苷酸环化酶大小变化。
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Forskolin requires more than the catalytic unit to activate adenylate cyclase.福司可林激活腺苷酸环化酶需要的不仅仅是催化单元。
Mol Cell Endocrinol. 1982 Nov-Dec;28(3):681-90. doi: 10.1016/0303-7207(82)90155-1.

引用本文的文献

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Effects of lead on adenylate cyclase activity in rat cerebral cortex.铅对大鼠大脑皮层腺苷酸环化酶活性的影响。
Neurochem Res. 1999 Aug;24(8):1037-42. doi: 10.1023/a:1021008910900.
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Forskolin suppresses seizures induced by pentylenetetrazol in mice.福司可林可抑制小鼠戊四氮诱发的癫痫发作。
Experientia. 1984 Nov 15;40(11):1270-1. doi: 10.1007/BF01946669.
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Ontogeny of adenosine 3',5'-monophosphate metabolism in guinea pig cerebral cortex. I. Development of responses to histamine, norepinephrine and adenosine.豚鼠大脑皮层中3',5'-环磷酸腺苷代谢的个体发生。I. 对组胺、去甲肾上腺素和腺苷反应的发育
Mol Cell Biochem. 1987 Feb;73(2):141-55. doi: 10.1007/BF00219428.
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Impaired cyclic nucleotide-mediated vasorelaxation may contribute to closure of the human umbilical artery after birth.环核苷酸介导的血管舒张功能受损可能导致出生后人类脐动脉关闭。
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