<i>myo</i>‐Inositol 1,4,5‐trisphosphorothioate is a potent competitive inhibitor of human erythrocyte 5‐phosphatase

Cooke, Allan M.; Nahorski, Stefan R.; Potter, Barry V. L.

doi:10.1016/0014-5793(89)80504-6

Cited by 51 publications

(19 citation statements)

References 17 publications

(10 reference statements)

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“…2,3 DPG in these cases evoked a small transient response, but again Finally, the phosphatase-resistant analogue DLinositol 1,4,5-trisphosphorothioate (Ins 1,4,5 P(S)3) was used (Cooke et al, 1987;Hamblin, Flora & Potter, 1987;Taylor et al, 1988). This analogue, as well as being a potent releaser of calcium, is a much more effective 5-phosphatase inhibitor than 2,3 DPG and has a Ki of 6 /,ZM (Cooke, Nahorski & Potter, 1989). Ins 1,4,5 P(S)3 (100 btM, corresponding to 50 >M of the D-form) evoked a transient response very similar to that seen when using Ins 1,4,5 P3 (Fig.…”

Section: Is the Transient Response To Ins 145 P3 Stimulation Due Tomentioning

confidence: 98%

Inositol 1,3,4,5-tetrakisphosphate is essential for sustained activation of the Ca2+-dependent K+ current in single internally perfused mouse lacrimal acinar cells

et al. 1989

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We have examined the effects of various inositol polyphosphates, alone and in combination, on the Ca2+-activated K+ current in internally perfused, single mouse lacrimal acinar cells. We used the patch-clamp technique for whole-cell current recording with a set-up allowing exchange of the pipette solution during individual experiments so that control and test periods could be directly compared in individual cells. Inositol 1,4,5-trisphosphate (Ins 1,4,5 P3) (10-100 microM) evoked a transient increase in the Ca2+-sensitive K+ current that was independent of the presence of Ca2+ in the external solution. The transient nature of the Ins 1,4,5 P3 effect was not due to rapid metabolic breakdown, as similar responses were obtained in the presence of 5 mM 2,3-diphosphoglyceric acid, that blocks the hydrolysis of Ins 1,4,5 P3, as well as with the stable analogue DL-inositol 1,4,5-trisphosphorothioate (Ins 1,4,5 P(S)3) (100 microM). Ins 1,3,4 P3 (50 microM) had no effect, whereas 50 microM Ins 2,4,5 P3 evoked responses similar to those obtained by 10 microM Ins 1,4,5 P3. A sustained increase in Ca2+-dependent K+ current was only observed when inositol 1,3,4,5-tetrakisphosphate (Ins 1,3,4,5 P4) (10 microM) was added to the Ins 1,4,5 P3 (10 microM)-containing solution and this effect could be terminated by removal of external Ca2+. The effect of Ins 1,3,4,5 P4 was specifically dependent on the presence of Ins 1,4,5 P3 as it was not found when 10 microM concentrations of Ins 1,3,4 P3 or Ins 2,4,5 P3 were used.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Is the Transient Response To Ins 145 P3 Stimulation Due Tomentioning

confidence: 98%

Inositol 1,3,4,5-tetrakisphosphate is essential for sustained activation of the Ca2+-dependent K+ current in single internally perfused mouse lacrimal acinar cells

et al. 1989

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“…5 demonstrate that the 3-kinase-insensitive 3-¯uoro analog of Ins(1,4,5)P 3 causes Ca 2+ release in stamen hair cells and is quickly inactivated, consistent with the absence of reports of Ins(1,4,5)P 3 3-kinase activity in plant cells. By contrast, when the 5-monophosphothioate analog of Ins(1,4,5)P 3 (Cooke et al 1989;Safrany et al 1991) was injected, a sustained elevation of [Ca 2+ ] was observed (Fig. 6), with little or no inactivation over the course of measurement.…”

Section: Discussionmentioning

confidence: 77%

Inositol 1,4,5 trisphosphate is inactivated by a 5-phosphatase in stamen hair cells of Tradescantia

DePass

Crain

Hepler

2001

Planta

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Inositol 1,4,5 trisphosphate [Ins(1,4,5)P3] is produced from the hydrolysis of phosphatidylinositol 4,5 bisphosphate, and as part of a second-messenger signal transduction mechanism, induces release of Ca2+ from internal stores in both plant and animal systems. It is less well established how the active Ins(1,4,5)P3 is inactivated. Studies in animal cells have demonstrated two separate metabolic pathways. Ins(1,4,5)P3 can be hydrolyzed by a 5-phosphatase or phosphorylated by a 3-kinase, resulting in the formation of Ins(1,4)P2 and Ins(1,3,4,5)P4, respectively, neither of which is able to mobilize intracellular Ca2+. Plant cell extracts have been reported to have hydrolytic and kinase activities that produce Ins(1,4)P2, and Ins(4,5)P2 and Ins(1,4,5,6)P4 from Ins(1,4,5)P3. These results offer little insight into the enzyme activities in the intact plant cell since the observed activities might be confined to intracellular compartments that have little if any impact on the signaling events within the cytosol that require Ins(1,4,5)P3. To resolve the mechanism of Ins(1,4,5)P3 inactivation, we microinjected stamen hair cells of Tradescantia virginiana L. with nonhydrolysable analogs of Ins(1,4,5)P3 that have been previously shown to cause Ca2+ release from intracellular stores. Our results indicate a sustained cytosolic [Ca2+] increase when cells were injected with the 5-phosphatase-insensitive 5-monophosphorothioate derivative of Ins(1,4,5)P3, in contrast to a brief transient when injected with the 3-kinase-insensitive 3-fluoro-3-deoxy Ins(1,4,5)P3 analog. We conclude that the 5-phosphatase pathway is the preferred pathway for Ins(1,4,5)P3 inactivation in the stamen hair cells of Tradescantia.

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“…i)i.-InsP,-SS is phosphorylated by this enzyme with a 'K5,,' similar to Ins( 1,4,S)P,; in contrast, i)i,-Ins ( 1,4,5)PS3 interacts only weakly with this enzyme and inhibits activity. This difference is likely to be due to the presence of the 4-phosphorothioate group in i)i,-Ins ( 1,4,5)pS3, which may disrupt the required orientation of the 3-hydroxyl group or interfere with access of the cosubstrate ATP to the 3-kinase active site [43,441. It is also noteworthy that total phosphorothioate substitution, in addition to making the analogue metabolism-resistant, also increases the potency of 5-phosphatase inhibition [43,441, and it is a matter of priority to establish whether the [,-isomer of inositol trisphosphorothioate ([,-Ins( 1,4,5)PS3) exhibits sufficient selectivity for the 5-phosphatase relative to other recognition sites to allow truly specific 5-phosphatase inhibition in cellular systems.…”

Section: Volume 19mentioning

confidence: 98%

Intracellular recognition sites for inositol 1,4,5-triphosphate and inositol 1,3,4,5-tetrakisphosphate

Challiss

Safrany

Potter

et al. 1991

Biochemical Society Transactions

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myo‐Inositol 1,4,5‐trisphosphorothioate is a potent competitive inhibitor of human erythrocyte 5‐phosphatase

Cited by 51 publications

References 17 publications

Inositol 1,3,4,5-tetrakisphosphate is essential for sustained activation of the Ca2+-dependent K+ current in single internally perfused mouse lacrimal acinar cells

Inositol 1,3,4,5-tetrakisphosphate is essential for sustained activation of the Ca2+-dependent K+ current in single internally perfused mouse lacrimal acinar cells

Inositol 1,4,5 trisphosphate is inactivated by a 5-phosphatase in stamen hair cells of Tradescantia

Intracellular recognition sites for inositol 1,4,5-triphosphate and inositol 1,3,4,5-tetrakisphosphate

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