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-(1,2,4,5)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 Ki value of as low as 1.4 microM, 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 microM. 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.
Hirata
M
M
Department of Biochemistry, Faculty of Dentistry, Kyushu University, Fukuoka, Japan.
Narumoto
N
N
Watanabe
Y
Y
Kanematsu
T
T
Koga
T
T
Ozaki
S
S
D000818:Animals; D001491:Basophils / Q000187:drug effects / Q000378:metabolism; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000201:enzymology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D004910:Erythrocyte Membrane / Q000201:enzymology; D006801:Humans; D006868:Hydrolysis; D015544:Inositol 1,4,5-Trisphosphate / Q000031:analogs & derivatives*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates / Q000138:chemical synthesis / Q000494:pharmacology*; D015471:Leukemia, Basophilic, Acute; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates; D018160:Receptors, Cytoplasmic and Nuclear; C081655:inositol-1,3,4,5-tetrakisphosphate; D015544:Inositol 1,4,5-Trisphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase; D010744:Phosphoric Monoester Hydrolases; D002118:Calcium