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Ca 2+ ‐mobilising properties of synthetic fluoro‐analogues of myo ‐inositol 1,4,5‐trisphosphate and their interaction with myo ‐inositol 1,4,5‐trisphosphate 3‐kinase and 5‐phosphatase
Author(s) -
Safrany Stephen T.,
Sawyer Deborah,
Wojcikiewicz Richard J.H.,
Nahorski Stefan R.,
Potter Barry V.L.
Publication year - 1990
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(90)80515-k
Subject(s) - inositol , chemistry , inositol trisphosphate , inositol phosphate , biochemistry , receptor
The ability of two fluoro‐analogues of D‐ myo ‐inositol 1,4,5‐trisphosphate (Ins(1,4,5)P 3 ) to mobilize intracellular Ca 2+ stores in SH‐SY5Y neuroblastoma cells has been investigated. DL‐2‐deoxy‐2‐fluoro‐ scyllo ‐Ins(1,4,5)P 3 (2F‐Ins(1,4,5)P 3 ) and DL‐2,2‐difluoro‐2‐deoxy‐ myo ‐Ins(1,4,5)P 3 (2,2‐F 2 ‐Ins(1,4,5)P 3 ) were full agonists (EC 50 s 0.77 and 0.41 μM respectively) and slightly less potent than D‐Ins(1,4,5)P 3 (EC 50 0.13 μM), indicating that the axial 2‐hydroxyl group of Ins(1,4,5)P 3 is relatively unimportant in receptor binding and stimulation of Ca 2+ release. Both analogues mobilized Ca 2+ with broadly similar kinetics and were substrates for Ins(1,4,5)P 3 3‐kinase but, qualitatively, were slightly poorer than Ins(1,4,5)P 3 . 2F‐Ins(1,4,5)P 3 was a weak substrate for Ins(1,4,5)P 3 5‐phosphatase but 2,2‐F 2 ‐Ins(1,4,5)P 3 was apparently not hydrolysed by this enzyme, although it inhibited its activity potently (K i = 26 μM).