myo-Inositol 1,4,5-trisphosphorothioate: a novel analogue of a biological second messenger

Cooke, Allan M.; Gigg, Roy; Potter, Barry V. L.

doi:10.1039/c39870001525

Cited by 67 publications

(31 citation statements)

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“…Ins 1,3,4,5,6 P5 was obtained from Boehringer, Mannheim. Ins 1,4,5 P(S)3 was prepared as described by Cooke, Gigg and Potter (1987). As Ins 1,4,5 P(S)3 is a racemic mixture of o-and L-enantiomers, the 100 ~M concentration used (Fig.…”

Section: Materials and Methods Resultsmentioning

confidence: 99%

“…In other experiments Ins !,4,5 P3 (10/~M) was introduced first, giving a transient response, and thereafter 2,3 DPG was added on top. 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).…”

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

confidence: 97%

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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: Materials and Methods Resultsmentioning

confidence: 99%

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

confidence: 97%

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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“…The influence of the difference in molecular weight on diffusion rate would be negligible, because the diffusion rate is affected by a factor of 1/cube root of molecular weight (Pusch & Neher, 1988 , and a flash pulse (at 300 V and 385 V of an available maximum) converted 1-2 and 2-4 % of the caged ATP, respectively, as estimated by high-performance liquid chromatography. (Cooke, Gigg & Potter, 1987) and was kindly given to us by him.…”

Section: Fluorescence Measurementsmentioning

confidence: 99%

Calcium release induced by inositol 1,4,5‐trisphosphate in single rabbit intestinal smooth muscle cells.

Komori

Bolton

1991

The Journal of Physiology

107

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SUMMARY1. Single smooth muscle cells were isolated by enzymic digestion from the longitudinal muscle layer of rabbit jejunum, and the response of the cells to calcium (Ca2+) release by InsP3 (D-myo-inositol 1,4,5-trisphosphate) was studied. Changes in internal Ca2+ concentration were monitored by measuring Ca2+-activated K+ currents (outward currents) using the whole-cell voltage-clamp technique.2. At break-through from cell-attached patch to whole-cell recording mode using a 100 /SM-InsP3-filled pipette, cells exhibited a brief outward current which reached its peak in 1-1 s and terminated within 10 s. Following this the generation of spontaneous transient outward currents (STOCs) was inhibited. (STOCs are considered to represent bursts of openings of Ca2+-activated K+ channels in response to spontaneous discharges of Ca2+ from the stores.) When a pipette filled with 20 /bMInsP3 was used, similar current responses were also evoked, but some cells failed to respond.3. The InsP3-induced outward current at membrane break-through was similar in size and time course to the outward current response of normal cells to bath-applied carbachol (CCh, 100 ,(M) or caffeine (20 mM).4. Dialysis with InsP3-containing solution inhibited the caffeine-induced outward current, depending on the pipette InsP3 concentration. Inclusion of heparin (5 mg/ml) in the pipette completely prevented inhibition by InsP3 of the caffeine response and of STOC discharge. However, the InsP3-induced current at breakthrough remained unchanged, probably because of the slower rate of diffusion of heparin.5. In cells dialysed with pipette solution containing 30 or 100 /LM-caged InsP3, flash photolysis (producing up to 1P5 ,SM-InsP3) induced an outward current response after a latency of 31-0 + 1-8 ms (n = 15), which was followed by inhibition of STOCs. The reversal potential of the current to flash-release of InsP3 followed closely the Nernst potential for K+ ions (EK), suggesting negligible contributions from channels other than Ca2+-activated K+ channels.

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“…Irvine of the AFRC Institute of Animal Physiology, Babraham, United Kingdom. DL-lns(1,4,5)P(S)3 was synthesized according to Cooke et al (1987) and was purified by ion-exchange chromatography. L-lns(1,4,5)P3 was inactive in causing oscillations when injected into Xenopus oocytes (Taylor et al, 1988).…”

Section: Methodsmentioning

confidence: 99%

Inositol trisphosphate analogues induce different oscillatory patterns in Xenopus oocytes.

Berridge¹,

Potter²

1990

Cell Regul

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Agonists that utilize the calcium-mobilizing second messenger inositol(1,4,5)trisphosphate Ins(1,4,5)P3 usually generate oscillations in intracellular calcium. Such oscillations, based on the periodic release of calcium from the endoplasmic reticulum, can also be induced by injecting cells with Ins(1,4,5)P3. The mechanism responsible for oscillatory activity was studied in Xenopus oocytes by injecting them with different inositol trisphosphates. The plasma membrane of Xenopus oocytes has calcium-dependent chloride channels that open in response to calcium, leading to membrane depolarization. Oscillations in calcium were thus monitored by recording membrane potential. The naturally occurring Ins(1,4,5)P3 produced a large initial transient followed by a single transient or a burst of oscillations. By contrast, two analogues (Ins(2,4,5)P3 and Ins(1,4,5)P(S)3) produced a different oscillatory pattern made up of a short burst of sharp transients. Ins(1,3,4,5)P4 had no effect when injected by itself, and it also failed to modify the oscillatory responses to either Ins(2,4,5)P3 or Ins(1,4,5)P(S)3. Both analogues failed to induce a response when injected immediately after the initial Ins(1,4,5)P3-induced response, indicating that they act on the same intracellular pool of calcium. The existence of different oscillatory patterns suggests that there may be different mechanisms for setting up calcium oscillations. The Ins(2,4,5)P3 and Ins(1,4,5)P(S)3 analogues may initiate oscillations through a negative feedback mechanism whereby calcium inhibits its own release. The two-pool model is the most likely mechanism to describe the Ins(1,4,5)P3-induced oscillations.

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myo-Inositol 1,4,5-trisphosphorothioate: a novel analogue of a biological second messenger

Abstract: m-myo-lnositol 1,4,5-trisphosphorothioate, a novel analogue of the biologically active second messenger D-myo-inositol 1,4,5-trisphosphate, has been synthesised by use of phosphite chemistry.

Cited by 67 publications

References 1 publication

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

Calcium release induced by inositol 1,4,5‐trisphosphate in single rabbit intestinal smooth muscle cells.

Inositol trisphosphate analogues induce different oscillatory patterns in Xenopus oocytes.

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