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肝癌细胞对儿茶酚胺反应性的研究。I. 大鼠腹水肝癌AH13细胞缺乏β-肾上腺素能反应性

Studies on responsiveness of hepatoma cells to catecholamines. I. Lack of beta-adrenergic responsiveness in rat ascites hepatoma AH13 cells.

作者信息

Matsunaga T, Takemoto N, Miyamoto K, Koshiura R

出版信息

Jpn J Pharmacol. 1984 Dec;36(4):499-506. doi: 10.1254/jjp.36.499.

DOI:10.1254/jjp.36.499
PMID:6098761
Abstract

The beta-adrenoceptor density and the activities of adenylate cyclase and cyclic AMP phosphodiesterase were examined to compare AH13 cells having lower beta-adrenergic responsiveness with other rat ascites hepatoma cells and normal rat liver cells. Normal rat liver cells used were cultured for 24 hr after the collagenase digestion of liver. The density of binding sites of 3H-dihydroalprenolol in AH13 cell plasma membrane was very similar to the density in AH44 and normal liver cell membrane, but that in AH130 cell plasma membrane was about 10-fold greater than those in the other three cell lines. The activity of cyclic AMP phosphodiesterase was about 2.5- to 7-fold higher in hepatoma cells than in rat liver cells, but this enzyme activity of AH13 cells was not especially high among the hepatoma cells examined. The basal adenylate cyclase activity was lower in AH44 cells, but was higher in AH13 and AH130 cells than in rat liver cells. However, adenylate cyclase of AH13 cells was hardly activated by isoproterenol, while the enzyme of the other cells was activated 3- to 5-fold. On the other hand, adenylate cyclase of each cell line including AH13 was activated 4- to 14-fold by NaF. From these results, it is suggested that AH13 cells can hardly produce cyclic AMP by the beta-adrenergic stimulation because of the disordered interaction of beta-adrenoceptors with adenylate cyclase.

摘要

检测β-肾上腺素能受体密度以及腺苷酸环化酶和环磷酸腺苷磷酸二酯酶的活性,以比较β-肾上腺素能反应性较低的AH13细胞与其他大鼠腹水肝癌细胞及正常大鼠肝细胞。所用正常大鼠肝细胞在肝脏经胶原酶消化后培养24小时。AH13细胞质膜中3H-二氢阿普洛尔结合位点的密度与AH44细胞及正常肝细胞膜中的密度非常相似,但AH130细胞质膜中的密度比其他三种细胞系中的密度大约高10倍。环磷酸腺苷磷酸二酯酶的活性在肝癌细胞中比在大鼠肝细胞中高约2.5至7倍,但在所检测的肝癌细胞中,AH13细胞的这种酶活性并非特别高。基础腺苷酸环化酶活性在AH44细胞中较低,但在AH13和AH130细胞中比在大鼠肝细胞中高。然而,AH13细胞的腺苷酸环化酶几乎不被异丙肾上腺素激活,而其他细胞的该酶被激活3至5倍。另一方面,包括AH13在内的每个细胞系的腺苷酸环化酶被氟化钠激活4至14倍。从这些结果表明,由于β-肾上腺素能受体与腺苷酸环化酶之间的相互作用紊乱,AH13细胞几乎不能通过β-肾上腺素能刺激产生环磷酸腺苷。

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