Mechanical stress induces release of ATP from Ehrlich ascites tumor cells

Pedersen, Susanne; Pedersen, Stine Falsig; Nilius, Bernd; Lambert, Ian Henry; Hoffmann, Else K.

doi:10.1016/s0005-2736(98)00228-4

Cited by 63 publications

(47 citation statements)

References 45 publications

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“…In EAT cells, this elicited Ca 2ϩ influx and activation of an outwardly rectifying whole cell current (783). ATP has been assigned a role as an autocrine messenger during RVD in rat hepatoma cells, such that ATP released during osmotic swelling binds to a purinergic receptor (subtype P2Y 1 ), eliciting a transient increase in [Ca 2ϩ ] i and consequently activation of Ca 2ϩ -sensitive K ϩ channels (189,420,421,1068).…”

Section: Atp As An Autocrine Messenger Inducing Ca 2ϩ Influxmentioning

confidence: 99%

Physiology of Cell Volume Regulation in Vertebrates

Hoffmann

Lambert²,

Pedersen³

2009

Physiological Reviews

1,307

1,677

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The ability to control cell volume is pivotal for cell function. Cell volume perturbation elicits a wide array of signaling events, leading to protective (e.g., cytoskeletal rearrangement) and adaptive (e.g., altered expression of osmolyte transporters and heat shock proteins) measures and, in most cases, activation of volume regulatory osmolyte transport. After acute swelling, cell volume is regulated by the process of regulatory volume decrease (RVD), which involves the activation of KCl cotransport and of channels mediating K+, Cl−, and taurine efflux. Conversely, after acute shrinkage, cell volume is regulated by the process of regulatory volume increase (RVI), which is mediated primarily by Na+/H+exchange, Na+-K+-2Cl−cotransport, and Na+channels. Here, we review in detail the current knowledge regarding the molecular identity of these transport pathways and their regulation by, e.g., membrane deformation, ionic strength, Ca2+, protein kinases and phosphatases, cytoskeletal elements, GTP binding proteins, lipid mediators, and reactive oxygen species, upon changes in cell volume. We also discuss the nature of the upstream elements in volume sensing in vertebrate organisms. Importantly, cell volume impacts on a wide array of physiological processes, including transepithelial transport; cell migration, proliferation, and death; and changes in cell volume function as specific signals regulating these processes. A discussion of this issue concludes the review.

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Section: Atp As An Autocrine Messenger Inducing Ca 2ϩ Influxmentioning

confidence: 99%

Physiology of Cell Volume Regulation in Vertebrates

Hoffmann

Lambert²,

Pedersen³

2009

Physiological Reviews

1,307

1,677

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“…To rule out the possible effects of unnoticed ATP release in the patch induced for mechanical stimulation (49,56,58,84), the ectonucleotidase apyrase (2 U/ml) was used in the pipette solution (plus LY) or in the bath (plus EB) when the cell membrane outside the patch was stimulated with 10 M ionomycin. There was no change attributable to apyrase in the single current recordings or in dye uptake in this condition (data not shown).…”

Section: Ionomycin Induced Fluorescent Dye Uptakementioning

confidence: 99%

Pharmacological properties of a pore induced by raising intracellular Ca²⁺

Faria¹,

Reis²,

Casabulho³

et al. 2009

American Journal of Physiology-Cell Physiology

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-Recent studies on the P2X 7 receptor in 2BH4 cells and peritoneal macrophages have demonstrated that the raise in intracellular Ca 2ϩ concentration induces a pore opening similar to P2X 7 receptor pore. Herein, we have investigated whether the pore activated by the elevation of intracellular Ca 2ϩ concentration is associated to P2X 7 receptor. Using patch clamp in cell attached, whole cell configuration, and dye uptake, we measured the pore opening in cell types that express the P2X 7 receptor (2BH4 cells and peritoneal macrophages) and in cells that do not express this receptor . In 2BH4 cells, the stimulation with ionomycin (5-10 M) increased intracellular free Ca 2ϩ concentration and induced pore formation with conductance of 421 Ϯ 14 pS, half-time (t 1 ⁄2) for ethidium bromide uptake of 118 Ϯ 17 s, and t 1 ⁄2 for Lucifer yellow of 122 Ϯ 11 s. P2X 7 receptor antagonists did not block these effects. Stimulation of HEK-293 and IT45-RI cells resulted in pore formation with properties similar to those found for 2BH4 cells. Connexin hemichannel inhibitors (carbenoxolone and heptanol) also did not inhibit the pore-induced effect following the increase in intracellular Ca 2ϩ concentration. However, 5-(N,N-hexamethylene)-amiloride, a P2X 7 receptor pore blocker, inhibited the induced pore. Moreover, intracellular signaling modulators, such as calmodulin, phospholipase C, mitogen-activated protein kinase, and cytoskeleton components were important for the pore formation. Additionally, we confirmed the results obtained for electrophysiology by using the flow cytometry, and we discarded the possibility of cellular death induced by raising intracellular Ca 2ϩ at the doses used by using lactate dehydrogenase release assay. In conclusion, increased concentration in intracellular Ca ϩ2 induces a novel membrane pore pharmacologically different from the P2X 7 associated pore and hemigap-junction pore.P2X 7 receptor; pore formation; second messenger P2X RECEPTORS are members of a family of P2 receptors with seven subtypes (P2X 1 -P2X 7 ) that induce an increase in intracellular Ca 2ϩ concentration when activated. Among the P2X receptors, P2X 7 subtype is the most divergent component of this family in terms of pharmacological properties, molecular structure, and function (54). This receptor forms a nonselective cation channel upon low ATP concentration, whereas at high ATP concentration, this receptor induces a pore formation that allows the flux of molecules of up to 900 Da and may lead to cell death. Although P2X 7 receptor is associated with expression of both functional channels and large pores, the structure of the large pore-forming subunits and whether the channel and the large pore are the same structure are still not known.From a physiological point of view, P2X 7 is mainly expressed in the immune system found in all cells of this system studied so far. The activation of P2X 7 receptor has several effects in the immune system such as release of mature interleukin-␤ and other pro-inflammatory cytokines (interleukin-18,...

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“…Due to its size and high density of charge, ATP cannot permeate membranes. However, release of ATP has been observed from a variety of cells, including tumor cells and lymphocytes, as well as from virtually all tissues under conditions of hypoxia, ischemia, inflammation, and cell necrosis (5)(6)(7)(8). The sources of released ATP include exocytotic granula from secretory cells, release from lysed cells, and nonlytic release from cytoplasmatic stores.…”

Section: Endritic Cells (Dc)mentioning

confidence: 99%

Extracellular ATP and TNF-α Synergize in the Activation and Maturation of Human Dendritic Cells

Schnurr

Then

Galambos

et al. 2000

The Journal of Immunology

174

140

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Extracellular ATP mediates numerous biological activities by interacting with plasma membrane P2 purinergic receptors. Recently, P2 receptors have been described on dendritic cells (DC), but their functional role remains unclear. Proposed functions include improved Ag presentation, cytokine production, chemotaxis, and induction of apoptosis. We investigated the effects of ATP and of other P2 receptor agonists on endocytosis, phenotype, IL-12 secretion, and T cell stimulatory capacity of human monocyte-derived DC. We found that in the presence of extracellular ATP, DC transiently increase their endocytotic activity. Subsequently, DC up-regulate CD86, CD54, and MHC-II; secrete IL-12; and exhibit an improved stimulatory capacity for allogeneic T cells. These effects were more pronounced when chemically modified ATP derivatives with agonistic activity on P2 receptors, which are resistent to degradation by ectonucleotidases, were applied. Furthermore, ATP and TNF-α synergized in the activation of DC. Stimulated with a combination of ATP and TNF-α, DC expressed the maturation marker CD83, secreted large amounts of IL-12, and were potent stimulators of T cells. In the presence of the P2 receptor antagonist suramin, the effects of ATP were completely abolished. Our results suggest that extracellular ATP may play an important immunomodulatory role by activating DC and by skewing the immune reaction toward a Th1 response through the induction of IL-12 secretion.

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Mechanical stress induces release of ATP from Ehrlich ascites tumor cells

Cited by 63 publications

References 45 publications

Physiology of Cell Volume Regulation in Vertebrates

Physiology of Cell Volume Regulation in Vertebrates

Pharmacological properties of a pore induced by raising intracellular Ca²⁺

Extracellular ATP and TNF-α Synergize in the Activation and Maturation of Human Dendritic Cells

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Mechanical stress induces release of ATP from Ehrlich ascites tumor cells

Cited by 63 publications

References 45 publications

Physiology of Cell Volume Regulation in Vertebrates

Physiology of Cell Volume Regulation in Vertebrates

Pharmacological properties of a pore induced by raising intracellular Ca2+

Extracellular ATP and TNF-α Synergize in the Activation and Maturation of Human Dendritic Cells

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Pharmacological properties of a pore induced by raising intracellular Ca²⁺