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

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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 (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.