合成的D-6-脱氧-肌醇1,4,5-三磷酸与释放Ca2+的D-肌醇1,4,5-三磷酸受体以及代谢酶5-磷酸酶和3-激酶之间的相互作用。

Interaction of synthetic D-6-deoxy-myo-inositol 1,4,5-trisphosphate with the Ca2(+)-releasing D-myo-inositol 1,4,5-trisphosphate receptor, and the metabolic enzymes 5-phosphatase and 3-kinase.

作者信息

Safrany S T, Wojcikiewicz R J, Strupish J, Nahorski S R, Dubreuil D, Cleophax J, Gero S D, Potter B V

机构信息

Department of Pharmacology and Therapeutics, University of Leicester, UK.

出版信息

FEBS Lett. 1991 Jan 28;278(2):252-6. doi: 10.1016/0014-5793(91)80128-p.

DOI:10.1016/0014-5793(91)80128-p

PMID:1846823

Abstract

The ability of D-6-deoxy-myo-inositol 1,4,5-trisphosphate [6-deoxy-Ins(1,4,5)P3], a synthetic analogue of the second messenger D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], to mobilise intracellular Ca2+ stores in permeabilised SH-SY5Y neuroblastoma cells was investigated. 6-Deoxy-Ins(1,4,5)P3 was a full agonist (EC50 = 6.4 microM), but was some 70-fold less potent than Ins (1,4,5)P3 (EC50 = 0.09 microM), indicating that the 6-hydroxyl group of Ins(1,4,5)P3 is important for receptor binding and stimulation of Ca2+ release, but is not an essential structural feature. 6-Deoxy-Ins(1,4,5)P3 was not a substrate for Ins (1,4,5)P3 5-phosphatase, but inhibited both the hydrolysis of 5-[32P]+ Ins (1,4,5)P3 (Ki 76 microM) and the phosphorylation of [3H]Ins(1,4,5)P3 (apparent Ki 5.7 microM). 6-Deoxy-Ins (1,4,5)P3 mobilized Ca2+ with different kinetics to Ins(1,4,5)P3, indicating that it is probably a substrate for Ins (1,4,5)P3 3-kinase.

摘要

研究了第二信使D-肌醇1,4,5-三磷酸[Ins(1,4,5)P3]的合成类似物D-6-脱氧-肌醇1,4,5-三磷酸[6-脱氧-Ins(1,4,5)P3]在通透的SH-SY5Y神经母细胞瘤细胞中动员细胞内钙储存的能力。6-脱氧-Ins(1,4,5)P3是一种完全激动剂（EC50 = 6.4 microM），但其效力比Ins(1,4,5)P3（EC50 = 0.09 microM）约低70倍，这表明Ins(1,4,5)P3的6-羟基对于受体结合和钙释放的刺激很重要，但不是必需的结构特征。6-脱氧-Ins(1,4,5)P3不是Ins(1,4,5)P3 5-磷酸酶的底物，但抑制5-[32P]+Ins(1,4,5)P3的水解（Ki 76 microM）和[3H]Ins(1,4,5)P3的磷酸化（表观Ki 5.7 microM）。6-脱氧-Ins(1,4,5)P3以与Ins(1,4,5)P3不同的动力学动员钙，表明它可能是Ins(1,4,5)P3 3-激酶的底物。