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

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.