Myo-inositol 1,3,4,5-tetrakisphosphate can independently mobilise intracellular calcium, via the inositol 1,4,5-trisphosphate receptor: studies with myo-inositol 1,4,5-trisphosphate-3-phosphorothioate and myo-inositol hexakisphosphate

Robert A. Wilcox; Emma M. Whitham; Changsheng Liu; Barry V.L. Potter; Stefan R. Nahorski

doi:10.1016/0014-5793(93)80817-E

Myo-inositol 1,3,4,5-tetrakisphosphate can independently mobilise intracellular calcium, via the inositol 1,4,5-trisphosphate receptor: studies with myo-inositol 1,4,5-trisphosphate-3-phosphorothioate and myo-inositol hexakisphosphate

Robert A. Wilcox
, Emma M. Whitham
, Changsheng Liu
, Barry V.L. Potter
, Stefan R. Nahorski

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

Myo-inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P₄] acts as a full agonist for Ca²⁺ release in saponin-permeabilised SH-SY5Y neuroblastoma cells. Studies were conducted in the presence of myo-inositol hexakisphosphate (InsP₆, 10 μM), to inhibit the Ins(1,3,4,5)P₄-3-phosphatase catalysed back conversion of Ins(1,3,4,5)P₄ to Ins(1,4,5)P₃. HPLC analysis confirmed that Ins(1,3,4,5)P₄ releases the entire content of Ins(1,4,5)P₃-sensitive intracellular Ca²⁺ stores, independent of 3-phosphatase activity. Further we utilised racemic myo-inositol 1,4,5-trisphosphate-3-phosphorothioate [dl-Ins(1,3,4,5)P₄-3S], a novel intrinsically Ins(1,3,4,5)P₄-3-phosphatase resistant Ins(1,3,4,5)P₄ analogue. DL-Ins(1,3,4,5)P₄-3S specifically displaced [³H]Ins(1,4,5)P₃ from bovine adrenal cortex Ins(1,4,5)P₃ binding sites (IC₅₀ = 889 nM, compared to Ins(1,4,5)P₃,1C₅₀ = 4.4 nM and Ins(1,3,4,5)P₄, IC₅₀ = 152 nM). dl-Ins(1,3,4,5)P₄-3S was a full agonist for Ca²⁺ release (EC₅₀ = 4.7 μM), being 90- and 2-fold less potent than Ins(1,4,5)P₃ and Ins(1,3,4,5)P₄ (with InsP₆), respectively. dl-Ins(1,3,4,5)P₄-3S will be an important tool for identification of potentially exclusive Ins(1,3,4,5)P₄ second messenger functions, since its resistance to 3-phosphatase action precludes the inconvenient artefact of steady state Ins(1,4,5)P₃ generation.

Original language	English
Pages (from-to)	267-271
Number of pages	5
Journal	FEBS Letters
Volume	336
Issue number	2
DOIs	https://doi.org/10.1016/0014-5793(93)80817-E
Publication status	Published - 27 Dec 1993
Externally published	Yes

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SDG 3 Good Health and Well-being

Keywords

Calcium mobilization
Inositol 1,3,4,5-tetrakisphosphate analogue
Inositol 1,3,4,5-tetrakisphosphate-3-phosphatase
Ins(1,4,5)P receptor
SH-SY5Y cell

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Wilcox, R. A., Whitham, E. M., Liu, C., Potter, B. V. L., & Nahorski, S. R. (1993). Myo-inositol 1,3,4,5-tetrakisphosphate can independently mobilise intracellular calcium, via the inositol 1,4,5-trisphosphate receptor: studies with myo-inositol 1,4,5-trisphosphate-3-phosphorothioate and myo-inositol hexakisphosphate. FEBS Letters, 336(2), 267-271. https://doi.org/10.1016/0014-5793(93)80817-E

@article{e64160d5d1a7477e880c87970cbe9d3b,

title = "Myo-inositol 1,3,4,5-tetrakisphosphate can independently mobilise intracellular calcium, via the inositol 1,4,5-trisphosphate receptor: studies with myo-inositol 1,4,5-trisphosphate-3-phosphorothioate and myo-inositol hexakisphosphate",

abstract = "Myo-inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] acts as a full agonist for Ca2+ release in saponin-permeabilised SH-SY5Y neuroblastoma cells. Studies were conducted in the presence of myo-inositol hexakisphosphate (InsP6, 10 μM), to inhibit the Ins(1,3,4,5)P4-3-phosphatase catalysed back conversion of Ins(1,3,4,5)P4 to Ins(1,4,5)P3. HPLC analysis confirmed that Ins(1,3,4,5)P4 releases the entire content of Ins(1,4,5)P3-sensitive intracellular Ca2+ stores, independent of 3-phosphatase activity. Further we utilised racemic myo-inositol 1,4,5-trisphosphate-3-phosphorothioate [dl-Ins(1,3,4,5)P4-3S], a novel intrinsically Ins(1,3,4,5)P4-3-phosphatase resistant Ins(1,3,4,5)P4 analogue. DL-Ins(1,3,4,5)P4-3S specifically displaced [3H]Ins(1,4,5)P3 from bovine adrenal cortex Ins(1,4,5)P3 binding sites (IC50 = 889 nM, compared to Ins(1,4,5)P3,1C50 = 4.4 nM and Ins(1,3,4,5)P4, IC50 = 152 nM). dl-Ins(1,3,4,5)P4-3S was a full agonist for Ca2+ release (EC50 = 4.7 μM), being 90- and 2-fold less potent than Ins(1,4,5)P3 and Ins(1,3,4,5)P4 (with InsP6), respectively. dl-Ins(1,3,4,5)P4-3S will be an important tool for identification of potentially exclusive Ins(1,3,4,5)P4 second messenger functions, since its resistance to 3-phosphatase action precludes the inconvenient artefact of steady state Ins(1,4,5)P3 generation.",

keywords = "Calcium mobilization, Inositol 1,3,4,5-tetrakisphosphate analogue, Inositol 1,3,4,5-tetrakisphosphate-3-phosphatase, Ins(1,4,5)P receptor, SH-SY5Y cell",

author = "Wilcox, \{Robert A.\} and Whitham, \{Emma M.\} and Changsheng Liu and Potter, \{Barry V.L.\} and Nahorski, \{Stefan R.\}",

year = "1993",

month = dec,

day = "27",

doi = "10.1016/0014-5793(93)80817-E",

language = "English",

volume = "336",

pages = "267--271",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "John Wiley \& Sons, Inc",

number = "2",

}

Wilcox, RA, Whitham, EM, Liu, C, Potter, BVL & Nahorski, SR 1993, 'Myo-inositol 1,3,4,5-tetrakisphosphate can independently mobilise intracellular calcium, via the inositol 1,4,5-trisphosphate receptor: studies with myo-inositol 1,4,5-trisphosphate-3-phosphorothioate and myo-inositol hexakisphosphate', FEBS Letters, vol. 336, no. 2, pp. 267-271. https://doi.org/10.1016/0014-5793(93)80817-E

Myo-inositol 1,3,4,5-tetrakisphosphate can independently mobilise intracellular calcium, via the inositol 1,4,5-trisphosphate receptor: studies with myo-inositol 1,4,5-trisphosphate-3-phosphorothioate and myo-inositol hexakisphosphate. / Wilcox, Robert A.; Whitham, Emma M.; Liu, Changsheng et al.
In: FEBS Letters, Vol. 336, No. 2, 27.12.1993, p. 267-271.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Myo-inositol 1,3,4,5-tetrakisphosphate can independently mobilise intracellular calcium, via the inositol 1,4,5-trisphosphate receptor

T2 - studies with myo-inositol 1,4,5-trisphosphate-3-phosphorothioate and myo-inositol hexakisphosphate

AU - Wilcox, Robert A.

AU - Whitham, Emma M.

AU - Liu, Changsheng

AU - Potter, Barry V.L.

AU - Nahorski, Stefan R.

PY - 1993/12/27

Y1 - 1993/12/27

N2 - Myo-inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] acts as a full agonist for Ca2+ release in saponin-permeabilised SH-SY5Y neuroblastoma cells. Studies were conducted in the presence of myo-inositol hexakisphosphate (InsP6, 10 μM), to inhibit the Ins(1,3,4,5)P4-3-phosphatase catalysed back conversion of Ins(1,3,4,5)P4 to Ins(1,4,5)P3. HPLC analysis confirmed that Ins(1,3,4,5)P4 releases the entire content of Ins(1,4,5)P3-sensitive intracellular Ca2+ stores, independent of 3-phosphatase activity. Further we utilised racemic myo-inositol 1,4,5-trisphosphate-3-phosphorothioate [dl-Ins(1,3,4,5)P4-3S], a novel intrinsically Ins(1,3,4,5)P4-3-phosphatase resistant Ins(1,3,4,5)P4 analogue. DL-Ins(1,3,4,5)P4-3S specifically displaced [3H]Ins(1,4,5)P3 from bovine adrenal cortex Ins(1,4,5)P3 binding sites (IC50 = 889 nM, compared to Ins(1,4,5)P3,1C50 = 4.4 nM and Ins(1,3,4,5)P4, IC50 = 152 nM). dl-Ins(1,3,4,5)P4-3S was a full agonist for Ca2+ release (EC50 = 4.7 μM), being 90- and 2-fold less potent than Ins(1,4,5)P3 and Ins(1,3,4,5)P4 (with InsP6), respectively. dl-Ins(1,3,4,5)P4-3S will be an important tool for identification of potentially exclusive Ins(1,3,4,5)P4 second messenger functions, since its resistance to 3-phosphatase action precludes the inconvenient artefact of steady state Ins(1,4,5)P3 generation.

AB - Myo-inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] acts as a full agonist for Ca2+ release in saponin-permeabilised SH-SY5Y neuroblastoma cells. Studies were conducted in the presence of myo-inositol hexakisphosphate (InsP6, 10 μM), to inhibit the Ins(1,3,4,5)P4-3-phosphatase catalysed back conversion of Ins(1,3,4,5)P4 to Ins(1,4,5)P3. HPLC analysis confirmed that Ins(1,3,4,5)P4 releases the entire content of Ins(1,4,5)P3-sensitive intracellular Ca2+ stores, independent of 3-phosphatase activity. Further we utilised racemic myo-inositol 1,4,5-trisphosphate-3-phosphorothioate [dl-Ins(1,3,4,5)P4-3S], a novel intrinsically Ins(1,3,4,5)P4-3-phosphatase resistant Ins(1,3,4,5)P4 analogue. DL-Ins(1,3,4,5)P4-3S specifically displaced [3H]Ins(1,4,5)P3 from bovine adrenal cortex Ins(1,4,5)P3 binding sites (IC50 = 889 nM, compared to Ins(1,4,5)P3,1C50 = 4.4 nM and Ins(1,3,4,5)P4, IC50 = 152 nM). dl-Ins(1,3,4,5)P4-3S was a full agonist for Ca2+ release (EC50 = 4.7 μM), being 90- and 2-fold less potent than Ins(1,4,5)P3 and Ins(1,3,4,5)P4 (with InsP6), respectively. dl-Ins(1,3,4,5)P4-3S will be an important tool for identification of potentially exclusive Ins(1,3,4,5)P4 second messenger functions, since its resistance to 3-phosphatase action precludes the inconvenient artefact of steady state Ins(1,4,5)P3 generation.

KW - Calcium mobilization

KW - Inositol 1,3,4,5-tetrakisphosphate analogue

KW - Inositol 1,3,4,5-tetrakisphosphate-3-phosphatase

KW - Ins(1,4,5)P receptor

KW - SH-SY5Y cell

UR - https://www.scopus.com/pages/publications/0027140497

U2 - 10.1016/0014-5793(93)80817-E

DO - 10.1016/0014-5793(93)80817-E

M3 - Article

C2 - 8262243

AN - SCOPUS:0027140497

SN - 0014-5793

VL - 336

SP - 267

EP - 271

JO - FEBS Letters

JF - FEBS Letters

IS - 2

ER -

Myo-inositol 1,3,4,5-tetrakisphosphate can independently mobilise intracellular calcium, via the inositol 1,4,5-trisphosphate receptor: studies with myo-inositol 1,4,5-trisphosphate-3-phosphorothioate and myo-inositol hexakisphosphate

Abstract

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Keywords

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