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纹状体和睾丸特异性磷酸二酯酶PDE10A:大鼠PDE10A的分离与特性研究

Striatum- and testis-specific phosphodiesterase PDE10A isolation and characterization of a rat PDE10A.

作者信息

Fujishige K, Kotera J, Omori K

机构信息

Discovery Research Laboratory, Tanabe Seiyaku Co. Ltd. Saitama, Japan.

出版信息

Eur J Biochem. 1999 Dec;266(3):1118-27. doi: 10.1046/j.1432-1327.1999.00963.x.

Abstract

PDE10A, a phosphodiesterase (PDE) exhibiting properties of a cAMP PDE and a cAMP-inhibited cGMP PDE, was cloned and investigated in detail in rats. PDE10A transcripts were abundant in the brain and testis. In situ hybridization analysis using a PDE10A riboprobe demonstrated the presence of PDE10A transcripts in the neurons of the striatum and the olfactory tubercle regions of the brain. Rat PDE10A cDNAs were isolated from a brain cDNA library and nucleotide sequence analysis revealed several N-terminal variants. The deduced amino-acid sequence of one of the major variant forms contained 794 amino acids, and it was 96% identical to that of the human PDE10A2. The other major form has a distinct N-terminal sequence that is not found in humans. PDE10A was partially purified from rat striatum and testis, and characterized with respect to Km, inhibitor sensitivity and immunoreactivity to an anti-PDE10A serum. These findings indicate that PDE10A functions in these tissues.

摘要

磷酸二酯酶10A(PDE10A)是一种兼具环磷酸腺苷(cAMP)磷酸二酯酶和cAMP抑制型环磷酸鸟苷(cGMP)磷酸二酯酶特性的磷酸二酯酶,已在大鼠中进行了克隆和详细研究。PDE10A转录本在脑和睾丸中大量存在。使用PDE10A核糖探针进行的原位杂交分析表明,在脑的纹状体神经元和嗅结节区域存在PDE10A转录本。从脑cDNA文库中分离出大鼠PDE10A cDNA,核苷酸序列分析揭示了几种N端变体。其中一种主要变体形式的推导氨基酸序列包含794个氨基酸,与人类PDE10A2的氨基酸序列有96%的同源性。另一种主要形式具有独特的N端序列,在人类中未发现。从大鼠纹状体和睾丸中部分纯化了PDE10A,并对其米氏常数(Km)、抑制剂敏感性以及抗PDE10A血清的免疫反应性进行了表征。这些发现表明PDE10A在这些组织中发挥作用。

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