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

FEBS Letters

Wojcikiewicz, R.J.H.²  Gero, S.D.¹  Safrany, S.T.²  Strupish, J.²  Cleophax, J.¹  Potter, B.V.L.³  Dubreuil, D.¹  Nahorski, S.R.² 

[1] Institut de Chimie des Substances Naturelles, CNRS, 91188 Gif-sur-Yvette Cedex, France;Department of Parmacology and Therapeutics, University of Leicester, Leicester, LE1 9HN, UK;School of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, UK

关键词: Second messenger;    Inositol phosphate analogue;    C2+ mobilisation;   

DOI  :  10.1016/0014-5793(91)80128-P

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 (EC₃₀ = 6.4 μM), but was some 70-fold less potent than Ins (1,4,5)P₃ (EC₃₀ = 0.09 μM), indicating that the 6-hydroxyl group of Ins(1,4,5)P₃ is most 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-[²²P] + Ins (1,4,5)P₃ (K ₁ 76 μM) and the phosphorylation of [³H]Ins(1,4,5)P₃ (apparent K ₁ 5.7 μM) 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.

【 授权许可】

Unknown