DL-myo-inositol 1,2,4,5-tetrakisphosphate, a potent analog of D-myo-inositol 1,4,5-trisphosphate

Synthetic DL-myo-inositol 1,2,4,5-tetrakisphosphate (DL-Ins-(1,2,4,S)P₄) functioned as a full agonist, with only 3-fold less potency than D-Ins(1,4,5)P₃ in eliciting the release of Ca²⁺ from nonmitochondrial pools of permeabilized rat basophilic leukemic cells. DL-Ins(1,2,4,5)P₄ inhibited the binding of D-[³H]InS(1,4,5)P₃ to the purified D-Ins(1,4,5)P₃ receptor with almost the same potency as seen for the Ca²⁺ release. This compound inhibited the hydrolysis of D-[³H]Ins(1,4,5)P₃ to D-[³H]Ins(1,4)P₂ catalyzed by erythrocyte ghosts, with a K_i value of as low as 1.4 μM, but it could not serve as a substrate for the same enzyme. D-Ins(1,4,5)P₃ 3-kinase in rat brain cytosol did not recognize the compound at concentrations up to 30 μM. Thus, it would appear that DL-Ins(1,2,4,5)P₄ can serve as a potent and long lasting experimental and pharmacological tool for stimulating D-Ins(1,4,5)P₃-mediating processes.