DL-myo-inositol 1,2,4,5-tetrakisphosphate, a potent analog of D-myo-inositol 1,4,5-trisphosphate
Hirata, M.; Narumoto, N.; Watanabe, Y.; Kanematsu, T.; Koga, T.; Ozaki, S.
Molecular Pharmacology 45(2): 271-276
1994
ISSN/ISBN: 0026-895X PMID: 8114676 Document Number: 435640
Synthetic DL-myo-inositol 1,2,4,5-tetrakisphosphate (DL-Ins(1,2,4,5)P-4) functioned as a full agonist, with only 3-fold less potency than D-Ins(1,4,5)P-3 in eliciting the release of Ca-2+ from nonmitochondrial pools of permeabilized rat basophilic leukemic cells. DL-Ins(1,2,4,5)P-4 inhibited the binding of D-(3H)Ins(1,4,5)P-3 to the purified D-Ins(1,4,5)P-3 receptor with almost the same potency as seen for the Ca-2+ release. This compound inhibited the hydrolysis of D-(3H)Ins(1,4,5)P-3 to D-(3H)Ins(1,4)P-2 catalyzed by erythrocyte ghosts, with a K-i value of as low as 1.4 mu-M, but it could not serve as a substrate for the same enzyme. D-Ins(1,4,5)P-3 3-kinase in rat brain cytosol did not recognize the compound at concentrations up to 30 mu-M. Thus, it would appear that DL-Ins(1,2,4,5)P-4 can serve as a potent and long lasting experimental and pharmacological tool for stimulating D-Ins(1,4,5)P-3-mediating processes.