Heparin inhibits inositol trisphosphate-induced calcium release from permeabilized rat liver cells

Hill, Tim; Berggren, Per Olof; Boynton, Alton L.

doi:10.1016/0006-291x(87)90492-x

Cited by 135 publications

(77 citation statements)

References 12 publications

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“…Heparin is a competitive inhibitor of the Ins(1,4,5)P 3 receptor that blocks Ins(1,4,5)P 3 -mediated store release (27). Ca completely ablated (Fig.…”

Section: Resultsmentioning

confidence: 94%

“…Consistent with recent evidence that the p110 subunits can have functionally distinct roles in intracellular signaling (22,25,26), we find that antibodies to p110␤ and p110␦, but not to p110␣, affect these two specific antigen-stimulated responses, despite the fact that all three subunits associate with tyrosine-phosphorylated proteins after receptor stimulation. Finally, we compare inhibition of Ca 2ϩ signaling in cells injected with PI 3-kinase-inhibitory antibodies to that in cells microinjected with heparin, which blocks binding of Ins(1,4,5)P 3 to its receptor (27), or with recombinant inositol polyphosphate 5-phosphatase I, which hydrolyzes Ins(1,4,5)P 3 . The results show that Fc⑀RI-mediated calcium responses are absolutely dependent on Ins(1,4,5)P 3 -mediated gating of its receptors on intracellular stores.…”

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confidence: 99%

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p110β and p110δ Phosphatidylinositol 3-Kinases Up-regulate FcεRI-activated Ca2+ Influx by Enhancing Inositol 1,4,5-Trisphosphate Production

Smith

Surviladze

Gaudet

et al. 2001

Journal of Biological Chemistry

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Fc⑀RI-induced Ca2؉ signaling in mast cells is initiated by activation of cytosolic tyrosine kinases. Here, in vitro phospholipase assays establish that the phosphatidylinositol 3-kinase (PI 3-kinase) lipid product, phosphatidylinositol 3,4,5-triphosphate, further stimulates phospholipase C␥2 that has been activated by conformational changes associated with tyrosine phosphorylation or low pH. A microinjection approach is used to directly assess the consequences of inhibiting class IA PI 3-kinases on Ca 2؉ responses after Fc⑀RI cross-linking in RBL-2H3 cells. Injection of antibodies to the p110␤ or p110␦ catalytic isoforms of PI 3-kinase, but not antibodies to p110␣, lengthens the lag time to release of Ca 2؉ stores and blunts the sustained phase of the calcium response. Ca 2؉ responses are also inhibited in cells microinjected with recombinant inositol polyphosphate 5-phosphatase I, which degrades inositol 1,4,5-trisphosphate (Ins(1,4,5)P 3 ), or heparin, a competitive inhibitor of the Ins(1,4,5)P 3 receptor. This indicates a requirement for Ins(1,4,5)P 3 to initiate and sustain Ca 2؉ responses even when PI 3-kinase is fully active. Antigeninduced cell ruffling, a calcium-independent event, is blocked by injection of p110␤ and p110␦ antibodies, but not by injection of 5-phosphatase I, heparin, or antip110␣ antibodies. These results suggest that the p110␤ and p110␦ isoforms of PI 3-kinase support Fc⑀RI-induced calcium signaling by modulating Ins(1,4,5)P 3 production, not by directly regulating the Ca 2؉ influx channel.Cross-linking of the high affinity receptor for IgE, Fc⑀RI, on mast cells results in the activation of tyrosine kinases Lyn and Syk, followed by tyrosine phosphorylation and activation of PLC␥ 1 isoforms and other downstream effectors (1). Subsequent hydrolysis of phosphatidylinositol 4,5-diphosphate by PLC␥ leads to the formation of Ins(1,4,5)P 3 , the release of Ca 2ϩ from internal stores (2), and the influx of Ca 2ϩ through storeoperated channels (3). Calcium influx, in turn, supports degranulation and the release of inflammatory mediators (4). This scenario was complicated in recent years by observations that PLC␥ activation and Ca 2ϩ responses and secretion are all diminished in mast cells treated with inhibitors of PI 3-kinases (5, 6). It was subsequently discovered that full activation of PLC␥ proteins in mast cells requires both tyrosine phosphorylation, potentially mediated by Tec family kinases (7), and interaction with the lipid products of PI 3-kinase (8). PtdIns(3,4,5)P 3 mediates membrane recruitment and phosphorylation of PLC␥1 in RBL-2H3 cells (8) and increases the activity of both PLC␥1 and PLC␥2 against lipid micelle substrates in vitro (9, 10).Despite demonstrated roles for PI 3-kinase in the activation of PLC␥, its specific contribution to the temporal regulation of Fc⑀RI-mediated Ca 2ϩ signaling is unresolved. Although wortmannin treatment can slightly increase the lag time leading to the initial rise in calcium after antigen stimulation, it does not block the initial response (1...

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“…Heparin is a competitive inhibitor of the Ins(1,4,5)P 3 receptor that blocks Ins(1,4,5)P 3 -mediated store release (27). Ca completely ablated (Fig.…”

Section: Resultsmentioning

confidence: 94%

mentioning

confidence: 99%

p110β and p110δ Phosphatidylinositol 3-Kinases Up-regulate FcεRI-activated Ca2+ Influx by Enhancing Inositol 1,4,5-Trisphosphate Production

Smith

Surviladze

Gaudet

et al. 2001

Journal of Biological Chemistry

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“…Heparin prevented the release of Ca stores by InsP3 in permeabilized liver cells (Hill, Berggren & Boynton, 1987). It also had this effect in a smooth muscle cell line (Ghosh, Eis, Mullaney, Ebert & Gill, 1988).…”

Section: Introductionmentioning

confidence: 92%

Role of G‐proteins in muscarinic receptor inward and outward currents in rabbit jejunal smooth muscle.

Komori

Bolton

1990

The Journal of Physiology

105

100

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SUMMARY1. Single smooth muscle cells obtained by enzymic dispersion of the longitudinal muscle layer of rabbit jejunum were held under voltage clamp using patch pipettes and membrane currents measured. The effects of carbachol or caffeine applied externally were examined in cells dialysed with normal pipette solutions or with a solution containing heparin (which blocks receptors for D-myo-inositol 1,4,5-trisphosphate, InsP3), guanosine 5-0-(y-thio)triphosphate (GTPyS) or guanosine 5-O-(/i-thio)diphosphate (GDPflS).2. Outward current in response to application of carbachol or caffeine was considered to represent the opening of calcium-activated potassium channels in response to a localized rise in the free ionized calcium concentration occasioned by the rapid discharge of stored calcium (Ca) by these agents.3. Heparin included in the pipette solution blocked outward current to muscarinic receptor activation by carbachol but not that to caffeine, suggesting that receptorevoked discharge of stored cellular Ca is caused by InsP3 action. However, heparin did not affect muscarinic-receptor inward current.4. After dialysis with 0-1-0{5 mM-GTPyS, carbachol inward current was evoked in two out of three of the cells; after dialysis with 0-1-0'2 mM-GTPyS for an average of 7-7 min it was 80 % of the normal response; after dialysis for an average of 8-6 min with 0 5 mM-GTPyS it was 31 % of the normal response. In contrast, 0 1 mM-GTPyS reduced caffeine outward current by 93 % after an average 4-5 min dialysis and spontaneous transient outward currents (STOCs) were abolished in 2-9 min on average.5. Carbachol inward current (at -40 or -50 mV) and carbachol outward current (at 0 mV) in responding cells were reduced only by half after 8-10 min dialysis with 1 mM-GDP,?S which has been shown in portal vein cells to antagonize the depletion of Ca stores by intracellular GTPyS (Komori & Bolton, 1989). After 8-10 min dialysis with 5 mM-GDP,8S outward current was 27 % of normal. However, if GDP/JS was present, outward current generally could not be evoked by a second application of carbachol.6. The discharge of Ca stores by dialysis with 01 mm-GTPyS was prevented completely by heparin included in the pipette solution, suggesting that activation of a G-protein associated with phospholipase C (PLC) enzyme accelerates PLC activity, MS 8003 S. KOMORI AND T. B. BOLTON InsP3 production and depletion of Ca stores. However, dialysis with GDP/?S or heparin did not affect Ca storage or discharge of STOCs suggesting that any tonic production of InsP3 is without effect on Ca storage and that InsP3 does not contribute to the cyclical process which gives rise to STOCs.7. The results suggest that a G-protein is associated with PLC and InsP3 production. Upon muscarinic receptor activation, InsP3 production is essential for Ca store release. The opening of cationic (inward current) channels in response to muscarinic receptor activation did not have properties typical of a G-proteinmediated system, and if a G-protein is involved it does not seem to...

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“…In control conditions (Figure 5a) (Hill et al, 1987;Ghosh et al, 1988) and to inhibit Ca2+ release via these receptors in smooth muscle cells (Komori & Bolton, 1990;Pacaud & Bolton, 1991 at which values the open-state probability of Ca2+ channels is high. The role of both Ca2 + channel activation and membrane depolarization evoked by Clcurrent in NA-induced contractions is illustrated by the effects of isradipine (a dihydropyridine derivative), 9-AC and ryanodine.…”

Section: Contraction Measurementsmentioning

confidence: 97%

Ca²⁺ channel activation and membrane depolarization mediated by Cl⁻ channels in response to noradrenaline in vascular myocytes

Pacaud

Loirand

Baron

et al. 1991

British J Pharmacology

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I The effects of noradrenaline (NA) were studied on vascular smooth muscle cells isolated from rat portal vein. 2 Two types of single-Ca2+ channel currents with conductances of 17pS and 8pS were obtained in cell-attached configuration. Bath application of NA increased the open probability of both channels during depolarizing pulses without a change of background membrane conductance. However, NA did not open Ca2 + channels when the membrane patch potential was held at -50mV, which is about the resting potential in physiological conditions. 3 In the whole-cell configuration, studies of voltage-dependent Ca2+ channel currents showed that the peak conductance curve was not shifted to more negative potentials by NA.4 Measurements of internal Ca2+-concentration ([Ca2+]) with Indo-1 indicated that NA increased [Ca2+] at a holding potential of -50 mV and evoked a Ca2 '-activated Cl-current. These effects were blocked when heparin was included in the pipette solution. 5 A Cl -channel blocker without effect on Ca2 + channels (anthracene-9-carboxylic acid) inhibited the contractions of portal vein strips induced by NA in a manner similar to that produced by a Ca2 + channel inhibitor (isradipine). The NA-induced contraction was completely suppressed in the presence of ryanodine which depletes intracellular Ca2 + stores. 6 The present study suggests that activation of Cl -channels by Ca2+ release produces a membrane depolarization which is a prerequisite for enhanced opening of voltage-dependent Ca2+ channels in response to NA in venous smooth muscle.

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Heparin inhibits inositol trisphosphate-induced calcium release from permeabilized rat liver cells

Cited by 135 publications

References 12 publications

p110β and p110δ Phosphatidylinositol 3-Kinases Up-regulate FcεRI-activated Ca2+ Influx by Enhancing Inositol 1,4,5-Trisphosphate Production

p110β and p110δ Phosphatidylinositol 3-Kinases Up-regulate FcεRI-activated Ca2+ Influx by Enhancing Inositol 1,4,5-Trisphosphate Production

Role of G‐proteins in muscarinic receptor inward and outward currents in rabbit jejunal smooth muscle.

Ca²⁺ channel activation and membrane depolarization mediated by Cl⁻ channels in response to noradrenaline in vascular myocytes

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Heparin inhibits inositol trisphosphate-induced calcium release from permeabilized rat liver cells

Cited by 135 publications

References 12 publications

p110β and p110δ Phosphatidylinositol 3-Kinases Up-regulate FcεRI-activated Ca2+ Influx by Enhancing Inositol 1,4,5-Trisphosphate Production

p110β and p110δ Phosphatidylinositol 3-Kinases Up-regulate FcεRI-activated Ca2+ Influx by Enhancing Inositol 1,4,5-Trisphosphate Production

Role of G‐proteins in muscarinic receptor inward and outward currents in rabbit jejunal smooth muscle.

Ca2+ channel activation and membrane depolarization mediated by Cl− channels in response to noradrenaline in vascular myocytes

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Ca²⁺ channel activation and membrane depolarization mediated by Cl⁻ channels in response to noradrenaline in vascular myocytes