Osmotic swelling‐induced ATP release: a new role for tyrosine and Rho‐kinases?

Grygorczyk, Ryszard; Guyot, Annick

doi:10.1111/j.1469-7793.2001.0582e.x

Cited by 16 publications

(18 citation statements)

References 8 publications

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“…Many cell types release ATP, and the mechanisms and physiological circumstances range from relatively well understood to quite controversial (see Refs. 51,135,161,191,407,485). Extracellular ATP acts on cell surface receptors of the P2X and P2Y types (53,347); it may be involved in phosphorylation reactions through ectokinases (110), and it is rapidly degraded by a series of cell surface enzymes to ADP, AMP, and adenosine (523), the last of which is taken back into cells by a specific transporter (9).…”

Section: Introductionmentioning

confidence: 99%

Molecular Physiology of P2X Receptors

North

2002

Physiological Reviews

2,683

128

3,397

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P2X receptors are membrane ion channels that open in response to the binding of extracellular ATP. Seven genes in vertebrates encode P2X receptor subunits, which are 40–50% identical in amino acid sequence. Each subunit has two transmembrane domains, separated by an extracellular domain (∼280 amino acids). Channels form as multimers of several subunits. Homomeric P2X1, P2X2, P2X3, P2X4, P2X5, and P2X7 channels and heteromeric P2X2/3 and P2X1/5 channels have been most fully characterized following heterologous expression. Some agonists (e.g., αβ-methylene ATP) and antagonists [e.g., 2′,3′- O-(2,4,6-trinitrophenyl)-ATP] are strongly selective for receptors containing P2X1 and P2X3subunits. All P2X receptors are permeable to small monovalent cations; some have significant calcium or anion permeability. In many cells, activation of homomeric P2X7 receptors induces a permeability increase to larger organic cations including some fluorescent dyes and also signals to the cytoskeleton; these changes probably involve additional interacting proteins. P2X receptors are abundantly distributed, and functional responses are seen in neurons, glia, epithelia, endothelia, bone, muscle, and hemopoietic tissues. The molecular composition of native receptors is becoming understood, and some cells express more than one type of P2X receptor. On smooth muscles, P2X receptors respond to ATP released from sympathetic motor nerves (e.g., in ejaculation). On sensory nerves, they are involved in the initiation of afferent signals in several viscera (e.g., bladder, intestine) and play a key role in sensing tissue-damaging and inflammatory stimuli. Paracrine roles for ATP signaling through P2X receptors are likely in neurohypophysis, ducted glands, airway epithelia, kidney, bone, and hemopoietic tissues. In the last case, P2X7 receptor activation stimulates cytokine release by engaging intracellular signaling pathways.

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Section: Introductionmentioning

confidence: 99%

Molecular Physiology of P2X Receptors

North

2002

Physiological Reviews

2,683

128

3,397

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“…These include E-NTPDases, a family of enzymes that hydrolyze nucleoside diphosphates and triphosphates, and also ecto-5Ј-nucleotidases that promote the dephosphorylation of monophosphate nucleotides. The coordinated action of E-NTPDases and 5Ј-nucleotidases reduces extracellular nucleotide levels and therefore restrains their action on P2 receptors.All cell types appear to possess mechanisms that enable a controlled, nonlytic release of ATP, that is, a release not involving cell membrane rupture, which occurs in response to osmotic, mechanical, and neurohormonal stimuli (17,22). As a consequence of this ATP efflux, cell surface ATP concentrations of up to 15 M can be achieved, levels sufficient to activate P2 receptors (29).…”

mentioning

confidence: 99%

“…All cell types appear to possess mechanisms that enable a controlled, nonlytic release of ATP, that is, a release not involving cell membrane rupture, which occurs in response to osmotic, mechanical, and neurohormonal stimuli (17,22). As a consequence of this ATP efflux, cell surface ATP concentrations of up to 15 M can be achieved, levels sufficient to activate P2 receptors (29).…”

mentioning

confidence: 99%

Kinetics of ATP release and cell volume regulation of hyposmotically challenged goldfish hepatocytes

Pafundo

Chara²,

Faillace³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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In most animal cells, hypotonic swelling is followed by a regulatory volume decrease (RVD) thought to prevent cell death. In contrast, goldfish hepatocytes challenged with hypotonic medium (180 mosM, HYPO) increase their volume 1.7 times but remain swollen and viable for at least 5 h. Incubation with ATP␥S (an ATP analog) in HYPO triggers a 42% volume decrease. This effect is concentration dependent (K1/2 ϭ 760 nM) and partially abolished by P2 receptor antagonists (64% inhibition). A similar induction of RVD is observed with ATP, UTP, and UDP, whereas adenosine inhibits RVD. Goldfish hepatocytes release more than 500 nM ATP during the first minutes of HYPO with no induction of RVD. The fact that similar concentrations of ATP␥S did trigger RVD could be explained by showing that ATP␥S induced ATP release. Finally, we observed that in a very small extracellular volume, hepatocytes do show a 56% RVD. This response was diminished by P2 receptor antagonists (73%) and increased (73%) when the extracellular ATP hydrolysis was inhibited 72%. Using a mathematical model, we predict that during the first 2 min of HYPO exposure the extracellular [ATP] is mainly governed by ATP diffusion and by both nonlytic and lytic ATP release, with almost no contribution from ecto-ATPase activity. We show that goldfish hepatocytes under standard HYPO (large volume) do not display RVD unless this is triggered by the addition of micromolar concentrations of nucleotides. However, under very low assay volumes, sufficient endogenous extracellular [ATP] can build up to induce RVD. extracellular ATP; water transport; ectonucleotidases MOST VERTEBRATE CELLS, when suddenly exposed to hypotonic conditions, rapidly swell due to the influx of water but subsequently, despite continuous osmotic perturbation, this swelling is opposed by the compensatory efflux of osmolytes and water. The resulting cell volume decrease is termed regulatory volume decrease, or RVD (20). RVD is mediated to a large extent by KCl loss through both K ϩ and Cl Ϫ channels, parallel activity of K ϩ -H ϩ and Cl Ϫ -HCO 3 Ϫ exchangers or KCl cotransporters (5, 21). However, little is known on the extracellular factors inducing RVD.In the past few years, a growing body of evidence has shown that extracellular nucleotides, mainly ATP, play a significant role in the control of cell volume regulation by binding to specific cell surface molecules termed "P" receptors (purinic and pyrimidinic receptors) (29). P1 receptors bind adenosine and other nucleosides, whereas P2 receptors bind mainly dinucleotides and trinucleotides. The P2 receptor family (8, 32, 36, 38) consists of two main subtypes, P2X and P2Y, representing ligand-gated cation channels and G protein-coupled receptors (linked to phospholipase C), respectively. At the cell membrane, the availability of agonists of P receptors is tightly regulated by specific membrane-bound enzymes located at the surface of the cell. These include E-NTPDases, a family of enzymes that hydrolyze nucleoside diphosphates and triphosphates, and also...

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“…Previous evidence suggests that VRAC may serve as a pathway for ATP release. Indeed, osmotic swelling induces ATP release from various cells that is inhibited by VRAC blockers (Grygorczyk and Guyot, 2001;Hisadome et al, 2002;Darby et al, 2003;Ullrich et al, 2006). Heptylamine inhibits VRAC, implying the existence of a VRAC-independent pathway for the heptylamine-induced release of ATP in NHEKs.…”

Section: Discussionmentioning

confidence: 99%

“…These metabolites include amino acids (e.g., glycine, glutamate, and aspartate), polyols, lactate, bicarbonate, and ATP (Grygorczyk and Guyot, 2001;Hisadome et al, 2002;Darby et al, 2003;Nilius and Droog-mans, 2003;Ullrich et al, 2006). VRACs also participate in the regulation of fundamental cell functions, particularly the regulatory volume decrease during cell swelling (Sardini et al, 2003) and the control of proliferation and apoptosis.…”

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confidence: 99%

The Amine-Containing Cutaneous Irritant Heptylamine Inhibits the Volume-Regulated Anion Channel and Mobilizes Intracellular Calcium in Normal Human Epidermal Keratinocytes

Raoux¹,

Colomban²,

Delmas³

et al. 2007

Mol Pharmacol

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Many amines are skin irritants and cause contact dermatitis. However, little is known about their mechanisms of action in keratinocytes except that they induce the release of the inflammatory mediators cytokines and ATP. Here, we tested whether volume-regulated anion channels (VRACs) in primary cultures of normal human epidermal keratinocytes are modulated by the referenced amine-containing cutaneous irritant heptylamine. Under isotonic conditions, we isolated the VRAC current (I VRAC ) from other conductances using a high Ca 2ϩ -buffering internal solution. I VRAC ran up after patch rupturing and reached a plateau within 15 min. It was reversibly and dose-dependently inhibited by heptylamine with an IC 50 value of 260 M. Cellswelling caused by the application of a hypotonic solution increased 2.7-fold I VRAC and reduced the inhibition of VRAC by heptylamine with a dose-response curve shifted approximately 10-fold to the right. In addition, we showed, using cell-attached patch recordings, that adding heptylamine to the bath inhibited VRAC activity. This suggests that heptylamine diffuses into the membrane to inhibit VRAC. Finally, we demonstrated that heptylamine induced Ca 2ϩ -store depletion and that VRAC inhibition was not caused by the increase in cytosolic Ca 2ϩ . Taken together, these results identify heptylamine as a blocker of VRAC and suggest that Ca 2ϩ -store depletion may be involved in mechanisms of irritant contact dermatitis caused by heptylamine.

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Osmotic swelling‐induced ATP release: a new role for tyrosine and Rho‐kinases?

Cited by 16 publications

References 8 publications

Molecular Physiology of P2X Receptors

Molecular Physiology of P2X Receptors

Kinetics of ATP release and cell volume regulation of hyposmotically challenged goldfish hepatocytes

The Amine-Containing Cutaneous Irritant Heptylamine Inhibits the Volume-Regulated Anion Channel and Mobilizes Intracellular Calcium in Normal Human Epidermal Keratinocytes

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