环磷酸腺苷磷酸二酯酶与表皮有丝分裂。

Cyclic AMP-phosphodiesterase and epidermal mitosis.

作者信息

Birnbaum J E, Sapp T M, Tolman E L

出版信息

J Invest Dermatol. 1976 Aug;67(2):235-9. doi: 10.1111/1523-1747.ep12513381.

Abstract

The relationship between cyclic AMP-phosphodiesterase (cAMP-PDE) inhibition and inhibition of epidermal mitosis was examined for several compounds using a soluble, low Km PDE activity from hairless mouse skin and the G2 mouse ear mitosis assay. Orders of potency determined at IC50 levels (concentrations required for 50% inhibition) were SQ 20009 greater than RO 20-1724 greater than papaverine greater than bufexamac greater than indomethacin greater than theophylline greater than p-biphenylylacetic acid greater than or less than glycyrrhetinic acid for inhibition of both PDE and mitosis. The disproportionately high antimitotic potency of puromycin relative to PDE inhibition was believed to reflect effects on protein biosynthesis. Activity of the three nonsteroidal anti-inflammatory agents (bufexamac, indomethacin, and p-biphenylylacetic acid) was unrelated to their effect on prostaglandin synthesis in homogenates of hairless mouse skin. The results suggest that the epidermal antimitotic activity of the compounds tested is related to their inhibition of cAMP-PDE and provide additional support for cAMP as a regulator of the G2 stage of the epidermal cell cycle.

摘要

利用来自无毛小鼠皮肤的可溶性低 Km 磷酸二酯酶（cAMP-PDE）活性和 G2 小鼠耳有丝分裂试验，研究了几种化合物的 cAMP-磷酸二酯酶（cAMP-PDE）抑制作用与表皮有丝分裂抑制之间的关系。在 IC50 水平（50%抑制所需浓度）测定的效力顺序为：对于 PDE 和有丝分裂的抑制，SQ 20009 ＞ RO 20-1724 ＞罂粟碱＞丁苯羟酸＞吲哚美辛＞茶碱＞对二苯基乙酸＞甘草次酸（大于或小于关系）。嘌呤霉素相对于 PDE 抑制的抗有丝分裂效力过高，被认为反映了对蛋白质生物合成的影响。三种非甾体抗炎药（丁苯羟酸、吲哚美辛和对二苯基乙酸）的活性与其对无毛小鼠皮肤匀浆中前列腺素合成的影响无关。结果表明，所测试化合物的表皮抗有丝分裂活性与其对 cAMP-PDE 的抑制作用有关，并为 cAMP 作为表皮细胞周期 G2 期调节剂提供了额外支持。