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

M Hirata, N Narumoto, Y Watanabe, T Kanematsu, T Koga and S Ozaki

Department of Biochemistry, Faculty of Dentistry, Kyushu University, Fukuoka, Japan.

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.

Volume 45, Issue 2, pp. 271-276, 02/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics




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S. K. Joseph, D. Boehning, S. Pierson, and C. V. Nicchitta
Membrane Insertion, Glycosylation, and Oligomerization of Inositol Trisphosphate Receptors in a Cell-free Translation System
J. Biol. Chem., January 17, 1997; 272(3): 1579 - 1588.
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Copyright © 1994 by the American Society for Pharmacology and Experimental Therapeutics