Ca2+‐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
- 10 December 1990
- journal article
- Published by Wiley in FEBS Letters
- Vol. 276 (1-2) , 91-94
- https://doi.org/10.1016/0014-5793(90)80515-k
Abstract
The ability of two fluoro‐analogues of D‐myo‐inositol 1,4,5‐trisphosphate (Ins(1,4,5)P3) to mobilize intracellular Ca2+ stores in SH‐SY5Y neuroblastoma cells has been investigated. DL‐2‐deoxy‐2‐fluoro‐scyllo‐Ins(1,4,5)P3 (2F‐Ins(1,4,5)P3) and DL‐2,2‐difluoro‐2‐deoxy‐myo‐Ins(1,4,5)P3 (2,2‐F2‐Ins(1,4,5)P3) were full agonists (EC50s 0.77 and 0.41 μM respectively) and slightly less potent than D‐Ins(1,4,5)P3 (EC50 0.13 μM), indicating that the axial 2‐hydroxyl group of Ins(1,4,5)P3 is relatively unimportant in receptor binding and stimulation of Ca2+ release. Both analogues mobilized Ca2+ with broadly similar kinetics and were substrates for Ins(1,4,5)P3 3‐kinase but, qualitatively, were slightly poorer than Ins(1,4,5)P3. 2F‐Ins(1,4,5)P3 was a weak substrate for Ins(1,4,5)P3 5‐phosphatase but 2,2‐F2‐Ins(1,4,5)P3 was apparently not hydrolysed by this enzyme, although it inhibited its activity potently (Ki = 26 μM).Keywords
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