Regulation of endocytic-transcytotic pathways and bile secretion by phosphatidylinositol 3-kinase in rats

Folli, Franco; Alvaro, Domenico; Gigliozzi, Alessandro; Bassotti, Cristina; Kahn, C. R.; Pontiroli, A. E.; Capocaccia, L.; Jézéquel, A.M.; Benedetti, Antonio

doi:10.1016/s0016-5085(97)70192-6

Cited by 46 publications

(34 citation statements)

References 8 publications

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“…10 Moreover, results in different models have implicated PI3-kinase as a modulator of vesicular trafficking, cytoskeletal organization, and bile formation, processes also directly influenced by physiologic changes in cell volume. 26 This partial list of volume-sensitive signaling events begs the question of how cell volume changes are sensed and transduced. While theories regarding molecular crowding, membrane tension, and stretch-activation of ion channels have been put forward, the jury is out.…”

Section: Volume-sensitive Signal Transductionmentioning

confidence: 99%

Liver Cell Volume Regulation: Size Matters

2001

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Liver cells are located in a critical anatomic site, with dual perfusion by both the portal and systemic circulations. Consequently, they are subject to unusually large changes in the concentrations of solutes such as amino acids, bile acids, and glucose between the fed and fasted states. Because these solutes are concentrated intracellularly, and osmolar gradients as low as ϳ1 mosm⅐L Ϫ1 are sufficient to induce transmembrane water movement, liver cell volume can increase by 5% to 10% in response to increased solute uptake. 1 These primary changes in volume are followed after a delay by compensatory increases in membrane ion permeability of 20-fold or more (Fig. 1), and the resulting shift toward net solute efflux represents a critical adaptive response that favors passive water movement and restoration of cell volume toward basal values. 2 Volume recovery is usually incomplete, however, and there is emerging evidence that the small residual differences from baseline, either positive or negative, act as a signal that directly influences a broad range of processes including kinase activation, gene expression, and membrane transport. 3 In this brief review, the emerging evidence supporting the presence of functional interactions between solute transport, intracellular metabolism, and cell volume is explored. Emphasis is placed on the role of ion channels and membrane transport in cell volume regulation, and the evolution of evidence that cell volume as a critical determinant of liver cell and organ function is summarized as well.

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Section: Volume-sensitive Signal Transductionmentioning

confidence: 99%

Liver Cell Volume Regulation: Size Matters

2001

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“…Moreover, results in different models have implicated PI 3-kinase as a modulator of vesicular trafficking, cytoskeletal organization, and bile formation, processes also directly influenced by physiologic changes in cell volume (46).…”

Section: Fig 6 Atp Overcomes the Inhibition Of Volume Recovery By Wmentioning

confidence: 99%

“…These observations imply that additional PI 3-kinase-independent mechanisms are operative as well. Given the important role for PI 3-kinase in regulation of endocytic and transcytotic pathways (46), it is attractive to speculate that ATP release may involve two separate pools of transporters, including transporters in the plasma membrane and those in submembrane vesicles. By interference with vesicle trafficking and cytoskeletal organization, wortmannin could decrease cellular ATP release by preventing insertion of new transporters from submembrane vesicles.…”

Section: Fig 6 Atp Overcomes the Inhibition Of Volume Recovery By Wmentioning

confidence: 99%

Phosphatidylinositol 3-Kinase Contributes to Cell Volume Regulation through Effects on ATP Release

Feranchak¹,

Roman²,

Schwiebert³

et al. 1998

Journal of Biological Chemistry

107

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Regulated changes in cell volume represent a signal that modulates a broad range of cell and organ functions. In HTC hepatoma cells, increases in volume are coupled to membrane ion permeability through a pathway involving (i) ATP efflux, (ii) autocrine stimulation of P 2 receptors, and (iii) increases in anion permeability and Cl ؊ efflux, contributing to recovery of volume toward basal values. Based on recent evidence that cell volume increases also stimulate phosphoinositide kinases, the purpose of these studies was to determine if phosphatidylinositol 3-kinase (PI 3-kinase) modulates these pathways. Exposure of cells to hypotonic buffer (20 or 40% less NaCl) caused an initial increase in cell volume and stimulated a rapid increase in ATP release. Subsequent opening of Cl ؊ channels was followed by recovery of cell volume toward basal values, despite the continuous presence of hypotonic buffer. Inhibition of PI 3-kinase with wortmannin (K i ‫؍‬ 3 nM) significantly inhibited both the rate of volume recovery and activation of Cl ؊ currents; similar results were obtained with LY294002 (10 M). Additionally, current activation was inhibited by intracellular dialysis with antibodies specific for the 110-kDa catalytic subunit of PI 3-kinase. Since release of ATP is a critical element in the volumeregulatory pathway, the role of PI 3-kinase on volumestimulated ATP release was assessed. Both wortmannin and LY294002 decreased basal and volume-stimulated ATP permeability but had no effect on the current response to exogenous ATP (10 M). These findings indicate that PI 3-kinase plays a significant role in regulation of cell volume and suggest that the effects are mediated in part through modulation of cellular ATP release.Polyphosphoinositides and their metabolites represent novel intracellular signaling molecules recently shown to mediate cellular responses to a number of hormones and growth factors (1-4). Activation of phosphatidylinositol (PI) 1 3-kinase leads to phosphorylation of phosphatidylinositol at the D-3 position of the inositol ring, representing a distinct pathway of PI metabolism. The 3-phosphorylated lipids rapidly increase upon growth factor stimulation, suggesting that they may act as second messengers mediating PI 3-kinase signals (2, 5-7).

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“…Phosphatidylinositol (PI) 3-kinase is a key element in transducing various actions of insulin on downstream effectors (19,20) and has been implicated in controlling vesicle trafficking and secretory function in many cell types (21)(22)(23)(24)(25)(26)(27). Pancreatic ␤-ells also contain PI 3-kinase activity (28 -30).…”

mentioning

confidence: 99%

Phosphatidylinositol 3-Kinase Suppresses Glucose-Stimulated Insulin Secretion by Affecting Post-Cytosolic [Ca2+] Elevation Signals

et al. 2002

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The role of phosphatidylinositol (PI) 3-kinase in the regulation of pancreatic ␤-cell function was investigated. PI 3-kinase activity in p85␣ regulatory subunitdeficient (p85␣ ؊/؊ ) islets was decreased to ϳ20% of that in wild-type controls. Insulin content and mass of rough endoplasmic reticula were decreased in ␤-cells from p85␣؊/؊ mice with increased insulin sensitivity. However, p85␣؊/؊ ␤-cells exhibited a marked increase in the insulin secretory response to higher concentrations of glucose. When PI 3-kinase in wild-type islets was suppressed by wortmannin or LY294002, the secretion was also substantially potentiated. Wortmannin's potentiating effect was not due to augmentation in glucose metabolism or cytosolic [Ca 2؉ ] elevation. Results of p85␣ ؊/؊ islets and wortmannin-treated wildtype islets stimulated with diazoxide and KCl showed that inhibition of PI 3-kinase activity exerted its effect on secretion, at least in part, distal to a cytosolic [Ca 2؉ ] elevation. These results suggest that PI 3-kinase activity normally plays a crucial role in the suppression of glucose-stimulated insulin secretion. Diabetes 51: 87-97, 2002

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Regulation of endocytic-transcytotic pathways and bile secretion by phosphatidylinositol 3-kinase in rats

Cited by 46 publications

References 8 publications

Liver Cell Volume Regulation: Size Matters

Liver Cell Volume Regulation: Size Matters

Phosphatidylinositol 3-Kinase Contributes to Cell Volume Regulation through Effects on ATP Release

Phosphatidylinositol 3-Kinase Suppresses Glucose-Stimulated Insulin Secretion by Affecting Post-Cytosolic [Ca2+] Elevation Signals

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