INHIBITION OF RECEPTOR-MEDIATED UPTAKE OF A LYSOSOMAL ENZYME INTO FIBROBLASTS BY CHLOROQUINE, PROCAINE AND AMMONIA

被引：82

作者：

SANDO, GN ^{[1
]}

TITUSDILLON, P ^{[1
]}

HALL, CW ^{[1
]}

NEUFELD, EF ^{[1
]}

机构：

[1] NIAMDD, HUMAN BIOCHEM GENET SECT, BETHESDA, MD 20014 USA

来源：

EXPERIMENTAL CELL RESEARCH | 1979年 / 119卷 / 02期

关键词：

D O I：

10.1016/0014-4827(79)90364-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cultured human skin fibroblasts take up α-l-iduronidase by receptor-mediated pinocytosis. Certain lysosomotropic amines such as chloroquine, ammonia and procaine inhibit this process, without affecting the fluid endocytosis of dextran. In contrast to the competitive inhibition by mannose 6-phosphate, the inhibition by amines is non-competitive and is therefore presumed not to affect binding of the enzyme to receptors. The dose response curves are very steep, and equations that best fit the data use a power of inhibitor concentration (i2 for procaine, i4 for chloroquine), indicating interaction of several amine molecules at the inhibitory site(s). The inhibition is reversed by removal of the amine from the medium and does not result from accelerated efflux of endocytosed enzyme. We suggest that the amines interfere with delivery of receptor-bound enzyme to lysosomes. © 1979.

引用

页码：359 / 364

页数：6

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