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培养的肾细胞(LLC PK1)产生1,25-二羟基胆钙化醇的C-24和C-23氧化代谢产物及其在体内肾脏中的存在情况。

Production of C-24- and C-23-oxidized metabolites of 1,25-dihydroxycholecalciferol by cultured kidney cells (LLC PK1) and their presence in kidney in vivo.

作者信息

Napoli J L, Martin C A

出版信息

Biochem J. 1984 May 1;219(3):713-7. doi: 10.1042/bj2190713.

Abstract

1,25-Dihydroxy[3H]cholecalciferol was converted into several more-polar metabolites by a cultured pig kidney cell line (LLC PK1). The production of metabolites was stimulated by pretreating the cells with unlabelled 1,25-dihydroxycholecalciferol. A similar profile of metabolites was observed on high-pressure-liquid-chromatographic analysis of an extract from the kidneys of rats dosed intravenously with 1,25-dihydroxy[3H]cholecalciferol. Among the metabolites detected were 1,24,25-trihydroxycholecalciferol, 1,25-dihydroxy-24-oxocholecalciferol, 1,23,25-trihydroxy-24-oxocholecalciferol and 1,25-dihydroxycholecalciferol-26,23-lactone. The results are in accord with data reported for intestinal 1,25-dihydroxycholecalciferol metabolism [Napoli, Pramanik, Royal, Reinhardt & Horst (1983) J. Biol. Chem. 258, 9100-9107]. These data indicate that C-23- and C-24-oxidation of 1,25-dihydroxycholecalciferol are phenomena common to calciferol target tissues, and that regulation of 1,25-dihydroxycholecalciferol homoeostasis is dependent on the rate of its metabolism in addition to the rate of its synthesis.

摘要

1,25-二羟基[3H]胆钙化醇被一种培养的猪肾细胞系(LLC PK1)转化为几种极性更强的代谢产物。用未标记的1,25-二羟基胆钙化醇预处理细胞可刺激代谢产物的产生。对静脉注射1,25-二羟基[3H]胆钙化醇的大鼠肾脏提取物进行高压液相色谱分析时,观察到了类似的代谢产物谱。检测到的代谢产物包括1,24,25-三羟基胆钙化醇、1,25-二羟基-24-氧代胆钙化醇、1,23,25-三羟基-24-氧代胆钙化醇和1,25-二羟基胆钙化醇-26,23-内酯。这些结果与报道的肠道1,25-二羟基胆钙化醇代谢的数据一致[那不勒斯、普拉马尼克、罗亚尔、莱因哈特和霍斯特(1983年)《生物化学杂志》258, 9100 - 9107]。这些数据表明,1,25-二羟基胆钙化醇的C-23和C-24氧化是维生素D靶组织共有的现象,并且1,25-二羟基胆钙化醇稳态的调节除了取决于其合成速率外,还取决于其代谢速率。

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