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Purinergic Signalling

, Volume 11, Issue 4, pp 533–550 | Cite as

ATP release, generation and hydrolysis in exocrine pancreatic duct cells

  • J. M. Kowal
  • G. G. Yegutkin
  • I. NovakEmail author
Original Article

Abstract

Extracellular adenosine triphosphate (ATP) regulates pancreatic duct function via P2Y and P2X receptors. It is well known that ATP is released from upstream pancreatic acinar cells. The ATP homeostasis in pancreatic ducts, which secrete bicarbonate-rich fluid, has not yet been examined. First, our aim was to reveal whether pancreatic duct cells release ATP locally and whether they enzymatically modify extracellular nucleotides/sides. Second, we wished to explore which physiological and pathophysiological factors may be important in these processes. Using a human pancreatic duct cell line, Capan-1, and online luminescence measurement, we detected fast ATP release in response to pH changes, bile acid, mechanical stress and hypo-osmotic stress. ATP release following hypo-osmotic stress was sensitive to drugs affecting exocytosis, pannexin-1, connexins, maxi-anion channels and transient receptor potential cation channel subfamily V member 4 (TRPV4) channels, and corresponding transcripts were expressed in duct cells. Direct stimulation of intracellular Ca2+ and cAMP signalling and ethanol application had negligible effects on ATP release. The released ATP was sequentially dephosphorylated through ecto-nucleoside triphosphate diphosphohydrolase (NTPDase2) and ecto-5′-nucleotidase/CD73 reactions, with respective generation of adenosine diphosphate (ADP) and adenosine and their maintenance in the extracellular medium at basal levels. In addition, Capan-1 cells express counteracting adenylate kinase (AK1) and nucleoside diphosphate kinase (NDPK) enzymes (NME1, 2), which contribute to metabolism and regeneration of extracellular ATP and other nucleotides (ADP, uridine diphosphate (UDP) and uridine triphosphate (UTP)). In conclusion, we illustrate a complex regulation of extracellular purine homeostasis in a pancreatic duct cell model involving: ATP release by several mechanisms and subsequent nucleotide breakdown and ATP regeneration via counteracting nucleotide-inactivating and nucleotide-phosphorylating ecto-enzymes. We suggest that extracellular ATP homeostasis in pancreatic ducts may be important in pancreas physiology and potentially in pancreas pathophysiology.

Keywords

Pannexin CD39 Ecto-nucleotidase Adenylate kinase UTP VNUT Connexin Pancreatitis 

Notes

Acknowledgments

We appreciate assistance of M. Zuccarini in autoradiographic assays and opportunity to use some of the facilities of S. Jalkanen’s laboratory. We are grateful to Prof. J. Hanrahan for providing us with the CFTR plasmid, Prof. Jean Sevigny for providing anti-NTPDase2 antibody and Prof. P. A. Pedersen and D. Sørensen for use of their facilities. The technical assistance of P. Roshof is greatly appreciated. Imaging experiments were done the Center for Advanced Bioimaging (CAB), University of Copenhagen, Denmark.

Author contribution

JMK performed all experiments and analysis on ATP release and enzyme activity. Enzyme assays were performed in collaboration with GY. IN performed imaging studies. The project was planned by IN, JMK and GY. The manuscript was written jointly by JMK and IN. All authors were involved in critically revising and approved the final version of the manuscript.

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

11302_2015_9472_MOESM1_ESM.pdf (338 kb)
ESM 1 (PDF 338 KB)

References

  1. 1.
    Lazarowski ER (2012) Vesicular and conductive mechanisms of nucleotide release. Purinergic Signal 8:359–373. doi: 10.1007/s11302-012-9304-9 PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Sawada K, Echigo N, Juge N, Miyaji T, Otsuka M, Omote H, Yamamoto A, Moriyama Y (2008) Identification of a vesicular nucleotide transporter. Proc Natl Acad Sci U S A 105:5683–5686. doi: 10.1073/pnas.0800141105 PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Baroja-Mazo A, Barbera-Cremades M, Pelegrin P (2013) The participation of plasma membrane hemichannels to purinergic signaling. Biochim Biophys Acta 1828:79–93. doi: 10.1016/j.bbamem.2012.01.002 CrossRefPubMedGoogle Scholar
  4. 4.
    Corriden R, Insel PA (2010) Basal release of ATP: an autocrine-paracrine mechanism for cell regulation. Sci Signal. doi: 10.1126/scisignal.3104re1 PubMedCentralPubMedGoogle Scholar
  5. 5.
    Yegutkin GG (2014) Enzymes involved in metabolism of extracellular nucleotides and nucleosides: functional implications and measurement of activities. Crit Rev Biochem Mol Biol 49:473–497. doi: 10.3109/10409238.2014.953627 CrossRefPubMedGoogle Scholar
  6. 6.
    Zimmermann H, Zebisch M, Strater N (2012) Cellular function and molecular structure of ecto-nucleotidases. Purinergic Signal 8:437–502. doi: 10.1007/s11302-012-9309-4 PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Novak I (2011) Purinergic signalling in epithelial ion transport: regulation of secretion and absorption. Acta Physiol (Oxf) 202:501–522. doi: 10.1111/j.1748-1716.2010.02225.x CrossRefGoogle Scholar
  8. 8.
    Burnstock G, Novak I (2012) Purinergic signalling in the pancreas in health and disease. J Endocrinol 213:123–141. doi: 10.1530/JOE-11-0434 CrossRefPubMedGoogle Scholar
  9. 9.
    Haanes KA, Kowal JM, Arpino G, Lange SC, Moriyama Y, Pedersen PA, Novak I (2014) Role of vesicular nucleotide transporter VNUT (SLC17A9) in release of ATP from AR42J cells and mouse pancreatic acinar cells. Purinergic Signal. doi: 10.1007/s11302-014-9406-7 PubMedCentralPubMedGoogle Scholar
  10. 10.
    Sorensen CE, Novak I (2001) Visualization of ATP release in pancreatic acini in response to cholinergic stimulus. Use of fluorescent probes and confocal microscopy. J Biol Chem 276:32925–32932. doi: 10.1074/jbc.M103313200 CrossRefPubMedGoogle Scholar
  11. 11.
    Haanes KA, Novak I (2010) ATP storage and uptake by isolated pancreatic zymogen granules. Biochem J 429:303–311. doi: 10.1042/BJ20091337 CrossRefPubMedGoogle Scholar
  12. 12.
    Wang J, Haanes KA, Novak I (2013) Purinergic regulation of CFTR and Ca2+-activated Cl channels and K+ channels in human pancreatic duct epithelium. Am J Physiol Cell Physiol 304:C673–C684. doi: 10.1152/ajpcell.00196.2012 CrossRefPubMedGoogle Scholar
  13. 13.
    Yegutkin GG, Samburski SS, Jalkanen S, Novak I (2006) ATP-consuming and ATP-generating enzymes secreted by pancreas. J Biol Chem 281:29441–29447. doi: 10.1074/jbc.M602480200 CrossRefPubMedGoogle Scholar
  14. 14.
    Sorensen CE, Amstrup J, Rasmussen HN, Ankorina-Stark I, Novak I (2003) Rat pancreas secretes particulate ecto-nucleotidase CD39. J Physiol 551:881–892. doi: 10.1113/jphysiol.2003.049411 PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Hegyi P, Petersen OH (2013) The exocrine pancreas: the acinar-ductal tango in physiology and pathophysiology. Rev Physiol Biochem Pharmacol 165:1–30. doi: 10.1007/112_2013_14 PubMedGoogle Scholar
  16. 16.
    Novak I, Haanes KA, Wang J (2013) Acid–base transport in pancreas—new challenges. Front Physiol 4:380. doi: 10.3389/fphys.2013.00380 PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    Kaunitz JD, Akiba Y (2011) Purinergic regulation of duodenal surface pH and ATP concentration: implications for mucosal defence, lipid uptake and cystic fibrosis. Acta Physiol (Oxf) 201:109–116. doi: 10.1111/j.1748-1716.2010.02156.x CrossRefGoogle Scholar
  18. 18.
    Wang J, Novak I (2013) Ion transport in human pancreatic duct epithelium, Capan-1 cells, is regulated by secretin, VIP, acetylcholine, and purinergic receptors. Pancreas 42:452–460. doi: 10.1097/MPA.0b013e318264c302 CrossRefPubMedGoogle Scholar
  19. 19.
    Wang J, Barbuskaite D, Tozzi M, Giannuzzo A, Sorensen CE, Novak I (2015) Proton pump inhibitors inhibit pancreatic secretion: role of gastric and Non-gastric H+/K+-ATPases. PLoS One 10:e0126432. doi: 10.1371/journal.pone.0126432 PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Lazarowski ER, Paradiso AM, Watt WC, Harden TK, Boucher RC (1997) UDP activates a mucosal-restricted receptor on human nasal epithelial cells that is distinct from the P2Y2 receptor. Proc Natl Acad Sci U S A 94:2599–2603PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Ouyang H, Mou L, Luk C, Liu N, Karaskova J, Squire J, Tsao MS (2000) Immortal human pancreatic duct epithelial cell lines with near normal genotype and phenotype. Am J Pathol 157:1623–1631. doi: 10.1016/S0002-9440(10)64800-6 PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Yegutkin GG, Henttinen T, Jalkanen S (2001) Extracellular ATP formation on vascular endothelial cells is mediated by ecto-nucleotide kinase activities via phosphotransfer reactions. FASEB J 15:251–260. doi: 10.1096/fj.00-0268com CrossRefPubMedGoogle Scholar
  23. 23.
    Helenius M, Jalkanen S, Yegutkin G (2012) Enzyme-coupled assays for simultaneous detection of nanomolar ATP, ADP, AMP, adenosine, inosine and pyrophosphate concentrations in extracellular fluids. Biochim Biophys Acta 1823:1967–1975. doi: 10.1016/j.bbamcr.2012.08.001 CrossRefPubMedGoogle Scholar
  24. 24.
    Okada SF, Nicholas RA, Kreda SM, Lazarowski ER, Boucher RC (2006) Physiological regulation of ATP release at the apical surface of human airway epithelia. J Biol Chem 281:22992–23002. doi: 10.1074/jbc.M603019200 PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Petersen OH, Sutton R (2006) Ca2+ signalling and pancreatitis: effects of alcohol, bile and coffee. Trends Pharmacol Sci 27:113–120. doi: 10.1016/j.tips.2005.12.006 CrossRefPubMedGoogle Scholar
  26. 26.
    Kowal JM, Haanes KA, Christensen NM, Novak I (2015) Bile acid effects are mediated by ATP release and purinergic signalling in exocrine pancreatic cells. Cell Commun Signal 13:28. doi: 10.1186/s12964-015-0107-9 PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    Boudreault F, Grygorczyk R (2004) Cell swelling-induced ATP release is tightly dependent on intracellular calcium elevations. J Physiol 561:499–513. doi: 10.1113/jphysiol.2004.072306 PubMedCentralCrossRefPubMedGoogle Scholar
  28. 28.
    Becker D, Blase C, Bereiter-Hahn J, Jendrach M (2005) TRPV4 exhibits a functional role in cell-volume regulation. J Cell Sci 118:2435–2440. doi: 10.1242/jcs.02372 CrossRefPubMedGoogle Scholar
  29. 29.
    Wu L, Gao X, Brown RC, Heller S, O’Neil RG (2007) Dual role of the TRPV4 channel as a sensor of flow and osmolality in renal epithelial cells. Am J Physiol Renal Physiol 293:F1699–F1713. doi: 10.1152/ajprenal.00462.2006 CrossRefPubMedGoogle Scholar
  30. 30.
    Mihara H, Boudaka A, Sugiyama T, Moriyama Y, Tominaga M (2011) Transient receptor potential vanilloid 4 (TRPV4)-dependent calcium influx and ATP release in mouse oesophageal keratinocytes. J Physiol 589:3471–3482. doi: 10.1113/jphysiol.2011.207829 PubMedCentralCrossRefPubMedGoogle Scholar
  31. 31.
    Hiasa M, Togawa N, Miyaji T, Omote H, Yamamoto A, Moriyama Y (2014) Essential role of vesicular nucleotide transporter in vesicular storage and release of nucleotides in platelets. Physiol Rep 10.14814/phy2.12034Google Scholar
  32. 32.
    Sprague RS, Ellsworth ML, Stephenson AH, Kleinhenz ME, Lonigro AJ (1998) Deformation-induced ATP release from red blood cells requires CFTR activity. Am J Physiol 275:H1726–H1732PubMedGoogle Scholar
  33. 33.
    Liu GJ, Werry EL, Bennett MR (2005) Secretion of ATP from Schwann cells in response to uridine triphosphate. Eur J Neurosci 21:151–160. doi: 10.1111/j.1460-9568.2004.03831.x CrossRefPubMedGoogle Scholar
  34. 34.
    Kringelbach TM, Aslan D, Novak I, Schwarz P, Jorgensen NR (2014) UTP-induced ATP release is a fine-tuned signalling pathway in osteocytes. Purinergic Signal 10:337–347. doi: 10.1007/s11302-013-9404-1 PubMedCentralCrossRefPubMedGoogle Scholar
  35. 35.
    Lazarowski ER, Harden TK (1999) Quantitation of extracellular UTP using a sensitive enzymatic assay. Br J Pharmacol 127:1272–1278. doi: 10.1038/sj.bjp.0702654 PubMedCentralCrossRefPubMedGoogle Scholar
  36. 36.
    Timoteo MA, Carneiro I, Silva I, Noronha-Matos JB, Ferreirinha F, Silva-Ramos M, Correia-de-Sa P (2014) ATP released via pannexin-1 hemichannels mediates bladder overactivity triggered by urothelial P2Y6 receptors. Biochem Pharmacol 87:371–379. doi: 10.1016/j.bcp.2013.11.007 CrossRefPubMedGoogle Scholar
  37. 37.
    Collavin L, Lazarevic D, Utrera R, Marzinotto S, Monte M, Schneider C (1999) wt p53 dependent expression of a membrane-associated isoform of adenylate kinase. Oncogene 18:5879–5888. doi: 10.1038/sj.onc.1202970 CrossRefPubMedGoogle Scholar
  38. 38.
    Ruan Q, Chen Y, Gratton E, Glaser M, Mantulin WW (2002) Cellular characterization of adenylate kinase and its isoform: two-photon excitation fluorescence imaging and fluorescence correlation spectroscopy. Biophys J 83:3177–3187. doi: 10.1016/S0006-3495(02)75320-4 PubMedCentralCrossRefPubMedGoogle Scholar
  39. 39.
    Lacombe ML, Milon L, Munier A, Mehus JG, Lambeth DO (2000) The human Nm23/nucleoside diphosphate kinases. J Bioenerg Biomembr 32:247–258CrossRefPubMedGoogle Scholar
  40. 40.
    Behrendorff N, Floetenmeyer M, Schwiening C, Thorn P (2010) Protons released during pancreatic acinar cell secretion acidify the lumen and contribute to pancreatitis in mice. Gastroenterology 139:1711–1720. doi: 10.1053/j.gastro.2010.07.051 CrossRefPubMedGoogle Scholar
  41. 41.
    Novak I, Praetorius J (2015) Fundamentals of bicarbonate secretion in epithelia. In: Kirk L. Hamilton, Daniel C. Devor, Brian J. Harvey (eds) Ion channels and transporters of epithelia in health and disease. SpringerGoogle Scholar
  42. 42.
    Sauter DR, Novak I, Pedersen SF, Larsen EH, Hoffmann EK (2014) ANO1 (TMEM16A) in pancreatic ductal adenocarcinoma (PDAC). Pflugers Arch. doi: 10.1007/s00424-014-1598-8 PubMedCentralPubMedGoogle Scholar
  43. 43.
    Ruan YC, Shum WW, Belleannee C, Da SN, Breton S (2012) ATP secretion in the male reproductive tract: essential role of CFTR. J Physiol 590:4209–4222. doi: 10.1113/jphysiol.2012.230581 PubMedCentralCrossRefPubMedGoogle Scholar
  44. 44.
    Reigada D, Mitchell CH (2005) Release of ATP from retinal pigment epithelial cells involves both CFTR and vesicular transport. Am J Physiol Cell Physiol 288:C132–C140. doi: 10.1152/ajpcell.00201.2004 PubMedGoogle Scholar
  45. 45.
    Yamamoto A, Ishiguro H, Ko SB, Suzuki A, Wang Y, Hamada H, Mizuno N, Kitagawa M, Hayakawa T, Naruse S (2003) Ethanol induces fluid hypersecretion from guinea-pig pancreatic duct cells. J Physiol 551:917–926. doi: 10.1113/jphysiol.2003.048827 PubMedCentralCrossRefPubMedGoogle Scholar
  46. 46.
    Maleth J, Balazs A, Pallagi P, Balla Z, Kui B, Katona M, Judak L, Nemeth I, Kemeny LV, Rakonczay Z Jr, Venglovecz V, Foldesi I, Peto Z, Somoracz A, Borka K, Perdomo D, Lukacs GL, Gray MA, Monterisi S, Zaccolo M, Sendler M, Mayerle J, Kuhn JP, Lerch MM, Sahin-Toth M, Hegyi P (2015) Alcohol disrupts levels and function of the cystic fibrosis transmembrane conductance regulator to promote development of pancreatitis. Gastroenterology 148:427–439. doi: 10.1053/j.gastro.2014.11.002 CrossRefPubMedGoogle Scholar
  47. 47.
    Pedersen SF, Kapus A, Hoffmann EK (2011) Osmosensory mechanisms in cellular and systemic volume regulation. J Am Soc Nephrol 22:1587–1597. doi: 10.1681/ASN.2010121284 CrossRefPubMedGoogle Scholar
  48. 48.
    Liu HT, Toychiev AH, Takahashi N, Sabirov RZ, Okada Y (2008) Maxi-anion channel as a candidate pathway for osmosensitive ATP release from mouse astrocytes in primary culture. Cell Res 18:558–565. doi: 10.1038/cr.2008.49 CrossRefPubMedGoogle Scholar
  49. 49.
    Islam MR, Uramoto H, Okada T, Sabirov RZ, Okada Y (2012) Maxi-anion channel and pannexin 1 hemichannel constitute separate pathways for swelling-induced ATP release in murine L929 fibrosarcoma cells. Am J Physiol Cell Physiol 303:C924–C935. doi: 10.1152/ajpcell.00459.2011 CrossRefPubMedGoogle Scholar
  50. 50.
    Seminario-Vidal L, Okada SF, Sesma JI, Kreda SM, van Heusden CA, Zhu Y, Jones LC, O’Neal WK, Penuela S, Laird DW, Boucher RC, Lazarowski ER (2011) Rho signaling regulates pannexin 1-mediated ATP release from airway epithelia. J Biol Chem 286:26277–26286. doi: 10.1074/jbc.M111.260562 PubMedCentralCrossRefPubMedGoogle Scholar
  51. 51.
    Sathe MN, Woo K, Kresge C, Bugde A, Luby-Phelps K, Lewis MA, Feranchak AP (2011) Regulation of purinergic signaling in biliary epithelial cells by exocytosis of SLC17A9-dependent ATP-enriched vesicles. J Biol Chem 286:25363–25376. doi: 10.1074/jbc.M111.232868 PubMedCentralCrossRefPubMedGoogle Scholar
  52. 52.
    Koizumi S, Fujishita K, Inoue K, Shigemoto-Mogami Y, Tsuda M, Inoue K (2004) Ca2+ waves in keratinocytes are transmitted to sensory neurons: the involvement of extracellular ATP and P2Y2 receptor activation. Biochem J 380:329–338. doi: 10.1042/BJ20031089 PubMedCentralCrossRefPubMedGoogle Scholar
  53. 53.
    Woo K, Dutta AK, Patel V, Kresge C, Feranchak AP (2008) Fluid flow induces mechanosensitive ATP release, calcium signalling and Cl- transport in biliary epithelial cells through a PKCzeta-dependent pathway. J Physiol 586:2779–2798. doi: 10.1113/jphysiol.2008.153015 PubMedCentralCrossRefPubMedGoogle Scholar
  54. 54.
    Takahara N, Ito S, Furuya K, Naruse K, Aso H, Kondo M, Sokabe M, Hasegawa Y (2014) Real-time imaging of ATP release induced by mechanical stretch in human airway smooth muscle cells. Am J Respir Cell Mol Biol 51:772–782. doi: 10.1165/rcmb.2014-0008OC CrossRefPubMedGoogle Scholar
  55. 55.
    Inoue K, Komatsu R, Imura Y, Fujishita K, Shibata K, Moriyama Y, Koizumi S (2014) Mechanism underlying ATP release in human epidermal keratinocytes. J Invest Dermatol 134:1465–1468. doi: 10.1038/jid.2013.516 CrossRefPubMedGoogle Scholar
  56. 56.
    Sipos A, Vargas SL, Toma I, Hanner F, Willecke K, Peti-Peterdi J (2009) Connexin 30 deficiency impairs renal tubular ATP release and pressure natriuresis. J Am Soc Nephrol 20:1724–1732. doi: 10.1681/ASN.2008101099 PubMedCentralCrossRefPubMedGoogle Scholar
  57. 57.
    Gomes P, Srinivas SP, Van DW, Vereecke J, Himpens B (2005) ATP release through connexin hemichannels in corneal endothelial cells. Invest Ophthalmol Vis Sci 46:1208–1218. doi: 10.1167/iovs.04-1181 CrossRefPubMedGoogle Scholar
  58. 58.
    Genetos DC, Kephart CJ, Zhang Y, Yellowley CE, Donahue HJ (2007) Oscillating fluid flow activation of gap junction hemichannels induces ATP release from MLO-Y4 osteocytes. J Cell Physiol 212:207–214. doi: 10.1002/jcp.21021 PubMedCentralCrossRefPubMedGoogle Scholar
  59. 59.
    Kanjanamekanant K, Luckprom P, Pavasant P (2014) P2X7 receptor-Pannexin1 interaction mediates stress-induced interleukin-1 beta expression in human periodontal ligament cells. J Periodontal Res 49:595–602. doi: 10.1111/jre.12139 CrossRefPubMedGoogle Scholar
  60. 60.
    Grygorczyk R, Furuya K, Sokabe M (2013) Imaging and characterization of stretch-induced ATP release from alveolar A549 cells. J Physiol 591:1195–1215. doi: 10.1113/jphysiol.2012.244145 PubMedCentralCrossRefPubMedGoogle Scholar
  61. 61.
    Yamamoto K, Furuya K, Nakamura M, Kobatake E, Sokabe M, Ando J (2011) Visualization of flow-induced ATP release and triggering of Ca2+ waves at caveolae in vascular endothelial cells. J Cell Sci 124:3477–3483. doi: 10.1242/jcs.087221 CrossRefPubMedGoogle Scholar
  62. 62.
    Reisin IL, Prat AG, Abraham EH, Amara JF, Gregory RJ, Ausiello DA, Cantiello HF (1994) The cystic fibrosis transmembrane conductance regulator is a dual ATP and chloride channel. J Biol Chem 269:20584–20591PubMedGoogle Scholar
  63. 63.
    Reddy MM, Quinton PM, Haws C, Wine JJ, Grygorczyk R, Tabcharani JA, Hanrahan JW, Gunderson KL, Kopito RR (1996) Failure of the cystic fibrosis transmembrane conductance regulator to conduct ATP. Science 271:1876–1879CrossRefPubMedGoogle Scholar
  64. 64.
    Grygorczyk R, Tabcharani JA, Hanrahan JW (1996) CFTR channels expressed in CHO cells do not have detectable ATP conductance. J Membr Biol 151:139–148CrossRefPubMedGoogle Scholar
  65. 65.
    Zhang WK, Wang D, Duan Y, Loy MM, Chan HC, Huang P (2010) Mechanosensitive gating of CFTR. Nat Cell Biol 12:507–512. doi: 10.1038/ncb2053 CrossRefPubMedGoogle Scholar
  66. 66.
    Yegutkin G, Bodin P, Burnstock G (2000) Effect of shear stress on the release of soluble ecto-enzymes ATPase and 5′-nucleotidase along with endogenous ATP from vascular endothelial cells. Br J Pharmacol 129:921–926. doi: 10.1038/sj.bjp.0703136 PubMedCentralCrossRefPubMedGoogle Scholar
  67. 67.
    Tatur S, Kreda S, Lazarowski E, Grygorczyk R (2008) Calcium-dependent release of adenosine and uridine nucleotides from A549 cells. Purinergic Signal 4:139–146. doi: 10.1007/s11302-007-9059-x PubMedCentralCrossRefPubMedGoogle Scholar
  68. 68.
    Lazarowski ER, Shea DA, Boucher RC, Harden TK (2003) Release of cellular UDP-glucose as a potential extracellular signaling molecule. Mol Pharmacol 63:1190–1197CrossRefPubMedGoogle Scholar
  69. 69.
    Blevins GT Jr, van de Westerlo EM, Williams JA (1994) Nucleoside diphosphate kinase associated with rat pancreatic membranes regulates CCK receptor affinity. Am J Physiol 267:G866–G874PubMedGoogle Scholar
  70. 70.
    Chu S, Xiong W, Zhang D, Soylu H, Sun C, Albensi BC, Parkinson FE (2013) Regulation of adenosine levels during cerebral ischemia. Acta Pharmacol Sin 34:60–66. doi: 10.1038/aps.2012.127 PubMedCentralCrossRefPubMedGoogle Scholar
  71. 71.
    Kordas KS, Sperlagh B, Tihanyi T, Topa L, Steward MC, Varga G, Kittel A (2004) ATP and ATPase secretion by exocrine pancreas in rat, guinea pig, and human. Pancreas 29:53–60CrossRefPubMedGoogle Scholar
  72. 72.
    Kittel A, Pelletier J, Bigonnesse F, Guckelberger O, Kordas K, Braun N, Robson SC, Sevigny J (2004) Localization of nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) and NTPDase2 in pancreas and salivary gland. J Histochem Cytochem 52:861–871. doi: 10.1369/jhc.3A6167.2004 CrossRefPubMedGoogle Scholar
  73. 73.
    Gonzalez DA, Egido P, Balcarcel NB, Hattab C, van Haaster MM, Pelletier J, Sevigny J, Ostuni MA (2015) Rat submandibular glands secrete nanovesicles with NTPDase and 5′-nucleotidase activities. Purinergic Signal 11:107–116. doi: 10.1007/s11302-014-9437-0 PubMedCentralCrossRefPubMedGoogle Scholar
  74. 74.
    Maksimow M, Kyhala L, Nieminen A, Kylanpaa L, Aalto K, Elima K, Mentula P, Lehti M, Puolakkainen P, Yegutkin GG, Jalkanen S, Repo H, Salmi M (2014) Early prediction of persistent organ failure by soluble CD73 in patients with acute pancreatitis*. Crit Care Med 42:2556–2564. doi: 10.1097/CCM.0000000000000550 CrossRefPubMedGoogle Scholar
  75. 75.
    Kunzli BM, Berberat PO, Giese T, Csizmadia E, Kaczmarek E, Baker C, Halaceli I, Buchler MW, Friess H, Robson SC (2007) Upregulation of CD39/NTPDases and P2 receptors in human pancreatic disease. Am J Physiol Gastrointest Liver Physiol 292:G223–G230. doi: 10.1152/ajpgi.00259.2006 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  1. 1.Department of Biology, Section for Cell Biology and PhysiologyUniversity of CopenhagenCopenhagen ØDenmark
  2. 2.Medicity Research Laboratory, Department of Medical Microbiology and ImmunologyUniversity of TurkuTurkuFinland

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