INTERACTION OF SYNTHETIC D-6-DEOXY-MYO-INOSITOL 1,4,5-TRISPHOSPHATE WITH THE CA-2+-RELEASING D-MYO-INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR, AND THE METABOLIC ENZYMES 5-PHOSPHATASE AND 3-KINASE

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-mu-M), but was some 70-fold less potent than Ins(1,4,5)P3 (EC50 = 0.09-mu-M), 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-[P-32] + Ins(1,4,5)P3 (K(i) 76-mu-M) and the phosphorylation of [H-3]Ins(1,4,5)P3 (apparent K(i) 5.7-mu-M). 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.