Negative feedback of extracellular ADP on ATP release in goldfish hepatocytes: a theoretical study.

A mathematical model was built to account for the kinetic of extracellular ATP (ATPe) and extracellular ADP (ADPe) concentrations from goldfish hepatocytes exposed to hypotonicity. The model was based on previous experimental results on the time course of ATPe accumulation, ectoATPase activity, and cell viability [Pafundo et al., 2008]. The kinetic of ATPe is controlled by a lytic ATP flux, a non-lytic ATP flux, and ecto-ATPase activity, whereas ADPe kinetic is governed by a lytic ADP flux and both ecto-ATPase and ecto-ADPase activities. Non-lytic ATPe efflux was included as a diffusion equation modulated by ATPe activation (positive feedback) and ADPe inhibition (negative feedback). The model yielded physically meaningful and stable steady-state solutions, was able to fit the experimental time evolution of ATPe and simulated the concomitant kinetic of ADPe. According to the model during the first minute of hypotonicity the concentration of ATPe is mainly governed by both lytic and non-lytic ATP efflux, with almost no contribution from ecto-ATPase activity. Later on, ecto-ATPase activity becomes important in defining the time dependent decay of ATPe levels. ADPe inhibition of the non-lytic ATP efflux was strong, whereas ATPe activation was minimal. Finally, the model was able to predict the consequences of partial inhibition of ecto-ATPase activity on the ATPe kinetic, thus emulating the exposure of goldfish cells to hypotonic medium in the presence of the ATP analog AMP-PCP. The model predicts this analog to both inhibit ectoATPase activity and increase non-lytic ATP release.

[1]  D. Häussinger,et al.  Functional significance of cell volume regulatory mechanisms. , 1998, Physiological reviews.

[2]  G. Dahl,et al.  Pannexin membrane channels are mechanosensitive conduits for ATP , 2004, FEBS letters.

[3]  S. Papa,et al.  Structural and functional characterization of F(o)F(1)-ATP synthase on the extracellular surface of rat hepatocytes. , 2008, Biochimica et biophysica acta.

[4]  Takahiro Shimizu,et al.  Receptor‐mediated control of regulatory volume decrease (RVD) and apoptotic volume decrease (AVD) , 2001, The Journal of physiology.

[5]  G. Dubyak,et al.  Methylene ATP analogs as modulators of extracellular ATP metabolism and accumulation , 2004, British journal of pharmacology.

[6]  T. Libermann,et al.  Nucleoside triphosphate diphosphohydrolase-2 (NTPDase2/CD39L1) is the dominant ectonucleotidase expressed by rat astrocytes , 2006, Neuroscience.

[7]  G. Dahl,et al.  A permeant regulating its permeation pore: inhibition of pannexin 1 channels by ATP. , 2009, American journal of physiology. Cell physiology.

[8]  J. Pearson,et al.  Kinetics of extracellular ATP hydrolysis by microvascular endothelial cells from rat heart. , 1995, The Biochemical journal.

[9]  T Kendall Harden,et al.  Mechanisms of release of nucleotides and integration of their action as P2X- and P2Y-receptor activating molecules. , 2003, Molecular pharmacology.

[10]  Timothy C Elston,et al.  Mathematical Model of Nucleotide Regulation on Airway Epithelia , 2008, Journal of Biological Chemistry.

[11]  B. Scharschmidt,et al.  Hepatocellular ATP-binding Cassette Protein Expression Enhances ATP Release and Autocrine Regulation of Cell Volume* , 1997, The Journal of Biological Chemistry.

[12]  Eric A. Barnard,et al.  International Union of Pharmacology LVIII: Update on the P2Y G Protein-Coupled Nucleotide Receptors: From Molecular Mechanisms and Pathophysiology to Therapy , 2006, Pharmacological Reviews.

[13]  C. Soeller,et al.  C-terminal splicing of NTPDase2 provides distinctive catalytic properties, cellular distribution and enzyme regulation. , 2005, The Biochemical journal.

[14]  Markus Ritter,et al.  Mechanisms Sensing and Modulating Signals Arising From Cell Swelling , 2002, Cellular Physiology and Biochemistry.

[15]  P. Cochard,et al.  Dual staining assessment of Schwann cell viability within whole peripheral nerves using calcein-AM and ethidium homodimer , 1997, Journal of Neuroscience Methods.

[16]  B. Locke,et al.  The effects of temperature, pH, and magnesium on the diffusion coefficient of ATP in solutions of physiological ionic strength. , 1996, Biochimica et biophysica acta.

[17]  G. Krumschnabel,et al.  Effects of extracellular nucleotides and their hydrolysis products on regulatory volume decrease of trout hepatocytes. , 2004, American journal of physiology. Regulatory, integrative and comparative physiology.

[18]  W. Wieser,et al.  Functional role of ecto-ATPase activity in goldfish hepatocytes. , 1998, The American journal of physiology.

[19]  Osvaldo Chara,et al.  Kinetics of ATP release and cell volume regulation of hyposmotically challenged goldfish hepatocytes. , 2008, American journal of physiology. Regulatory, integrative and comparative physiology.

[20]  A. Harris,et al.  Connexins: A guide , 2009 .

[21]  G. Burnstock,et al.  Purine and pyrimidine receptors , 2007, Cellular and Molecular Life Sciences.

[22]  R. Swanson,et al.  ATP‐induced ATP release from astrocytes , 2003, Journal of neurochemistry.

[23]  R. Grygorczyk,et al.  Cell swelling‐induced ATP release is tightly dependent on intracellular calcium elevations , 2004, The Journal of physiology.

[24]  M. L. Ellsworth,et al.  Participation of cAMP in a signal-transduction pathway relating erythrocyte deformation to ATP release. , 2001, American journal of physiology. Cell physiology.

[25]  S. Bezrukov,et al.  ATP transport through a single mitochondrial channel, VDAC, studied by current fluctuation analysis. , 1998, Biophysical journal.

[26]  Osvaldo Chara,et al.  Kinetics of Extracellular ATP from Goldfish Hepatocytes: A Lesson from Mathematical Modeling , 2009, Bulletin of mathematical biology.

[27]  A. Harris,et al.  Pannexins or connexins , 2009 .

[28]  Herbert Zimmermann.  Signalling via ATP in the nervous system , 1994, Trends in Neurosciences.

[29]  M. Colombini,et al.  VDAC channels mediate and gate the flow of ATP: implications for the regulation of mitochondrial function. , 1997, Biophysical journal.

[30]  G. Dahl,et al.  Activation of pannexin 1 channels by ATP through P2Y receptors and by cytoplasmic calcium , 2006, FEBS letters.

[31]  R. Sabirov,et al.  ATP release via anion channels , 2005, Purinergic Signalling.

[32]  Jens Leipziger,et al.  ATP release from non-excitable cells , 2009, Purinergic Signalling.

[33]  R. Roman,et al.  Volume-sensitive purinergic signaling in human hepatocytes. , 2000, Journal of hepatology.

[34]  H. Ollivier,et al.  Effects of hypo‐osmotic stress on ATP release in isolated turbot (Scophthalmus maximus) hepatocytes , 2006, Biology of the cell.

[35]  G. Dubyak,et al.  Autocrine ATP release coupled to extracellular pyrophosphate accumulation in vascular smooth muscle cells. , 2009, American journal of physiology. Cell physiology.

[36]  K. Alleva,et al.  Identification of two distinct E-NTPDases in liver of goldfish (Carassius auratus L.). , 2002, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[37]  Seiko F. Okada,et al.  Physiological Regulation of ATP Release at the Apical Surface of Human Airway Epithelia*♦ , 2006, Journal of Biological Chemistry.

[38]  G. Dubyak,et al.  Colocalization of ATP Release Sites and Ecto-ATPase Activity at the Extracellular Surface of Human Astrocytes* , 2003, Journal of Biological Chemistry.