Purinergic Signalling

, Volume 8, Issue 3, pp 359–373 | Cite as

Vesicular and conductive mechanisms of nucleotide release

  • Eduardo R. LazarowskiEmail author


Extracellular nucleotides and nucleosides promote a vast range of physiological responses, via activation of cell surface purinergic receptors. Virtually all tissues and cell types exhibit regulated release of ATP, which, in many cases, is accompanied by the release of uridine nucleotides. Given the relevance of extracellular nucleotide/nucleoside-evoked responses, understanding how ATP and other nucleotides are released from cells is an important physiological question. By facilitating the entry of cytosolic nucleotides into the secretory pathway, recently identified vesicular nucleotide and nucleotide–sugar transporters contribute to the exocytotic release of ATP and UDP-sugars not only from endocrine/exocrine tissues, but also from cell types in which secretory granules have not been biochemically characterized. In addition, plasma membrane connexin hemichannels, pannexin channels, and less-well molecularly defined ATP conducting anion channels have been shown to contribute to the release of ATP (and UTP) under a variety of conditions.


ATP release Extracellular nucleotides UDP-sugars Exocytosis VNUT Connexins Pannexins 



Solute carrier


Vesicular nucleotide transporter






Small interfering RNA


Short hairpin RNA


1,2-Bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid




5-Nitro-2-(3-phenylpropylamino)benzoic acid





We thank Lisa Brown for editorial assistance of the manuscript. Supported by National Institute of Health grant P01-HL034322.

Conflict of interest statement

The author has no potential conflict of interest.


  1. 1.
    Burnstock G (2006) Purinergic signalling. Br J Pharmacol 147(Suppl 1):S172–S181PubMedGoogle Scholar
  2. 2.
    Khakh BS, North RA (2006) P2X receptors as cell-surface ATP sensors in health and disease. Nature 442:527–532PubMedGoogle Scholar
  3. 3.
    von Kügelgen I, Harden TK (2011) Molecular pharmacology, physiology, and structure of the P2Y receptors. Adv Pharmacol 61:373–415Google Scholar
  4. 4.
    Gessi S, Merighi S, Varani K, Borea PA (2011) Adenosine receptors in health and disease. Adv Pharmacol 61:41–75PubMedGoogle Scholar
  5. 5.
    Yegutkin GG (2008) Nucleotide- and nucleoside-converting ectoenzymes: important modulators of purinergic signalling cascade. Biochim Biophys Acta 1783:673–694PubMedGoogle Scholar
  6. 6.
    Corriden R, Insel PA (2010) Basal release of ATP: an autocrine–paracrine mechanism for cell regulation. Sci Signal 3:re1–re25PubMedGoogle Scholar
  7. 7.
    Praetorius HA, Leipziger J (2009) ATP release from non-excitable cells. Purinergic Signal 5:433–446PubMedGoogle Scholar
  8. 8.
    Lazarowski ER, Boucher RC, Harden TK (2003) Mechanisms of release of nucleotides and integration of their action as P2X- and P2Y-receptor activating molecules. Mol Pharmacol 64:785–795PubMedGoogle Scholar
  9. 9.
    Demidchik V, Nichols C, Oliynyk M, Dark A, Glover BJ, Davies JM (2003) Is ATP a signaling agent in plants? Plant Physiol 133:456–461PubMedGoogle Scholar
  10. 10.
    Chara O, Espelt MV, Krumschnabel G, Schwarzbaum PJ (2011) Regulatory volume decrease and P receptor signaling in fish cells: mechanisms, physiology, and modeling approaches. J Exp Zool A Ecol Genet Physiol 315:175–202PubMedGoogle Scholar
  11. 11.
    Kukulski F, Levesque SA, Sevigny J (2011) Impact of ectoenzymes on p2 and p1 receptor signaling. Adv Pharmacol 61:263–299PubMedGoogle Scholar
  12. 12.
    Robson SC, Sevigny J, Zimmermann H (2006) The E-NTPDase family of ectonucleotidases: structure function relationships and pathophysiological significance. Purinergic Signal 2:409–430PubMedGoogle Scholar
  13. 13.
    Lazarowski ER, Sesma JI, Seminario-Vidal L, Kreda SM (2011) Molecular mechanisms of purine and pyrimidine nucleotide release. Adv Pharmacol 61:221–261PubMedGoogle Scholar
  14. 14.
    Zimmermann H (2008) ATP and acetylcholine, equal brethren. Neurochem Int 52:634–648PubMedGoogle Scholar
  15. 15.
    Evans RJ, Derkach V, Surprenant A (1992) ATP mediates fast synaptic transmission in mammalian neurons. Nature 357:503–505PubMedGoogle Scholar
  16. 16.
    Evans RJ, Surprenant A (1992) Vasoconstriction of guinea-pig submucosal arterioles following sympathetic nerve stimulation is mediated by the release of ATP. Br J Pharmacol 106:242–249PubMedGoogle Scholar
  17. 17.
    Burnstock G (1997) The past, present and future of purine nucleotides as signalling molecules. Neuropharmacology 36:1127–1139PubMedGoogle Scholar
  18. 18.
    Dean GE, Fishkes H, Nelson PJ, Rudnick G (1984) The hydrogen ion-pumping adenosine triphosphatase of platelet dense granule membrane. Differences from F1F0- and phosphoenzyme-type ATPases. J Biol Chem 259:9569–9574PubMedGoogle Scholar
  19. 19.
    Gualix J, Abal M, Pintor J, Garcia-Carmona F, Miras-Portugal MT (1996) Nucleotide vesicular transporter of bovine chromaffin granules. Evidence for a mnemonic regulation. J Biol Chem 271:1957–1965PubMedGoogle Scholar
  20. 20.
    Gualix J, Pintor J, Miras-Portugal MT (1999) Characterization of nucleotide transport into rat brain synaptic vesicles. J Neurochem 73:1098–1104PubMedGoogle Scholar
  21. 21.
    Kanner BI, Schuldiner S (1987) Mechanism of transport and storage of neurotransmitters. CRC Crit Rev Biochem 22:1–38PubMedGoogle Scholar
  22. 22.
    Anderson P, Rohlich P, Slorach SA, Uvnas B (1974) Morphology and storage properties of rat mast cell granules isolated by different methods. Acta Physiol Scand 91:145–153PubMedGoogle Scholar
  23. 23.
    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 276:32925–32932PubMedGoogle Scholar
  24. 24.
    Aberer W, Kostron H, Huber E, Winkler H (1978) A characterization of the nucleotide uptake of chromaffin granules of bovine adrenal medulla. Biochem J 172:353–360PubMedGoogle Scholar
  25. 25.
    Winkler H (1976) The composition of adrenal chromaffin granules: an assessment of controversial results. Neuroscience 1:65–80PubMedGoogle Scholar
  26. 26.
    Bankston LA, Guidotti G (1996) Characterization of ATP transport into chromaffin granule ghosts—synergy of ATP and serotonin accumulation in chromaffin granule ghosts. J Biol Chem 271:17132–17138PubMedGoogle Scholar
  27. 27.
    Hanada H, Moriyama Y, Maeda M, Futai M (1990) Kinetic studies of chromaffin granule H+-ATPase and effects of bafilomycin A1. Biochem Biophys Res Commun 170:873–878PubMedGoogle Scholar
  28. 28.
    Burgoyne RD, Morgan A (2003) Secretory granule exocytosis. Physiol Rev 83:581–632PubMedGoogle Scholar
  29. 29.
    Chapman ER, An S, Barton N, Jahn R (1994) SNAP-25, a t-SNARE which binds to both syntaxin and synaptobrevin via domains that may form coiled coils. J Biol Chem 269:27427–27432PubMedGoogle Scholar
  30. 30.
    Li JY, Jahn R, Dahlstrom A (1996) Axonal transport and targeting of the t-SNAREs SNAP-25 and syntaxin 1 in the peripheral nervous system. Eur J Cell Biol 70:12–22PubMedGoogle Scholar
  31. 31.
    Rettig J, Neher E (2002) Emerging roles of presynaptic proteins in Ca++-triggered exocytosis. Science 298:781–785PubMedGoogle Scholar
  32. 32.
    Zhang X, Kim-Miller MJ, Fukuda M, Kowalchyk JA, Martin TF (2002) Ca2+-dependent synaptotagmin binding to SNAP-25 is essential for Ca2+-triggered exocytosis. Neuron 34:599–611PubMedGoogle Scholar
  33. 33.
    Chaineau M, Danglot L, Galli T (2009) Multiple roles of the vesicular-SNARE TI-VAMP in post-Golgi and endosomal trafficking. FEBS Lett 583:3817–3826PubMedGoogle Scholar
  34. 34.
    Reimer RJ, Edwards RH (2004) Organic anion transport is the primary function of the SLC17/type I phosphate transporter family. Pflugers Arch 447:629–635PubMedGoogle Scholar
  35. 35.
    Sreedharan S, Shaik JH, Olszewski PK, Levine AS, Schioth HB, Fredriksson R (2010) Glutamate, aspartate and nucleotide transporters in the SLC17 family form four main phylogenetic clusters: evolution and tissue expression. BMC Genomics 11:17PubMedGoogle Scholar
  36. 36.
    Fredriksson R, Nordstrom KJ, Stephansson O, Hagglund MG, Schioth HB (2008) The solute carrier (SLC) complement of the human genome: phylogenetic classification reveals four major families. FEBS Lett 582:3811–3816PubMedGoogle Scholar
  37. 37.
    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 105:5683–5686PubMedGoogle Scholar
  38. 38.
    Tokunaga A, Tsukimoto M, Harada H, Moriyama Y, Kojima S (2010) Involvement of SLC17A9-dependent vesicular exocytosis in the mechanism of ATP release during T cell activation. J Biol Chem 285:17406–17416PubMedGoogle Scholar
  39. 39.
    Iwatsuki K, Ichikawa R, Hiasa M, Moriyama Y, Torii K, Uneyama H (2009) Identification of the vesicular nucleotide transporter (VNUT) in taste cells. Biochem Biophys Res Commun 388:1–5PubMedGoogle Scholar
  40. 40.
    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 589:3471–3482PubMedGoogle Scholar
  41. 41.
    Novak I (2008) Purinergic receptors in the endocrine and exocrine pancreas. Purinergic Signal 4:237–253PubMedGoogle Scholar
  42. 42.
    Chander A, Johnson RG, Reicherter J, Fisher AB (1986) Lung lamellar bodies maintain an acidic internal pH. J Biol Chem 261:6126–6131PubMedGoogle Scholar
  43. 43.
    Costa JL, Fay DD, Kirk KL (1984) Quinacrine and basic amines in human platelets: subcellular compartmentation and effects on serotonin. Res Commun Chem Pathol Pharmacol 43:25–42PubMedGoogle Scholar
  44. 44.
    Di A, Krupa B, Bindokas VP, Chen Y, Brown ME, Palfrey HC, Naren AP, Kirk KL, Nelson DJ (2002) Quantal release of free radicals during exocytosis of phagosomes. Nat Cell Biol 4:279–285PubMedGoogle Scholar
  45. 45.
    Kolber MA, Henkart PA (1988) Quantitation of secretion by rat basophilic leukemia cells by measurements of quinacrine uptake. Biochim Biophys Acta 939:459–466PubMedGoogle Scholar
  46. 46.
    Goren MB, Swendsen CL, Fiscus J, Miranti C (1984) Fluorescent markers for studying phagosome-lysosome fusion. J Leukoc Biol 36:273–292PubMedGoogle Scholar
  47. 47.
    Haanes KA, Novak I (2010) ATP storage and uptake by isolated pancreatic zymogen granules. Biochem J 429:303–311PubMedGoogle Scholar
  48. 48.
    Lazarowski ER, Boucher RC (2009) Purinergic receptors in airway epithelia. Curr Opin Pharmacol 9:262–267PubMedGoogle Scholar
  49. 49.
    Kreda SM, Okada SF, van Heusden CA, O'Neal W, Gabriel S, Abdullah L, Davis CW, Boucher RC, Lazarowski ER (2007) Coordinated release of nucleotides and mucin from human airway epithelial Calu-3 cells. J Physiol 584:245–259PubMedGoogle Scholar
  50. 50.
    Okada SF, Zhang L, Kreda SM, Abdullah LH, Davis CW, Pickles RJ, Lazarowski ER, Boucher RC (2011) Coupled nucleotide and mucin hypersecretion from goblet cell metaplastic human airway epithelium. Am J Respir Cell Mol Biol 45:253–260PubMedGoogle Scholar
  51. 51.
    Kreda SM, Seminario-Vidal L, van Heusden CA, O'Neal W, Jones L, Boucher RC, Lazarowski ER (2010) Receptor-promoted exocytosis of airway epithelial mucin granules containing a spectrum of adenine nucleotides. J Physiol 588:2255–2267PubMedGoogle Scholar
  52. 52.
    Leitner JW, Sussman KE, Vatter AE, Schneider FH (1975) Adenine nucleotides in the secretory granule fraction of rat islets. Endocrinology 96:662–677PubMedGoogle Scholar
  53. 53.
    Hutton JC, Penn EJ, Peshavaria M (1983) Low-molecular-weight constituents of isolated insulin-secretory granules. Bivalent cations, adenine nucleotides and inorganic phosphate. Biochem J 210:297–305PubMedGoogle Scholar
  54. 54.
    Detimary P, Jonas JC, Henquin JC (1996) Stable and diffusible pools of nucleotides in pancreatic islet cells. Endocrinology 137:4671–4676PubMedGoogle Scholar
  55. 55.
    Obermuller S, Lindqvist A, Karanauskaite J, Galvanovskis J, Rorsman P, Barg S (2005) Selective nucleotide-release from dense-core granules in insulin-secreting cells. J Cell Sci 118:4271–4282PubMedGoogle Scholar
  56. 56.
    Karanauskaite J, Hoppa MB, Braun M, Galvanovskis J, Rorsman P (2009) Quantal ATP release in rat beta-cells by exocytosis of insulin-containing LDCVs. Pflugers Arch 458:389–401PubMedGoogle Scholar
  57. 57.
    Bulanova E, Bulfone-Paus S (2010) P2 receptor-mediated signaling in mast cell biology. Purinergic Signal 6:3–17PubMedGoogle Scholar
  58. 58.
    Osipchuk Y, Cahalan M (1992) Cell-to-cell spread of calcium signals mediated by ATP receptors in mast cells. Nature 359:241–244PubMedGoogle Scholar
  59. 59.
    Uvnas B (1974) The molecular basis for the storage and release of histamine in rat mast cell granules. Life Sci 14:2355–2366PubMedGoogle Scholar
  60. 60.
    Smith-Garvin JE, Koretzky GA, Jordan MS (2009) T cell activation. Annu Rev Immunol 27:591–619PubMedGoogle Scholar
  61. 61.
    Schenk U, Westendorf AM, Radaelli E, Casati A, Ferro M, Fumagalli M, Verderio C, Buer J, Scanziani E, Grassi F (2008) Purinergic control of T cell activation by ATP released through pannexin-1 hemichannels. Sci Signal 1:ra6PubMedGoogle Scholar
  62. 62.
    Yip L, Woehrle T, Corriden R, Hirsh M, Chen Y, Inoue Y, Ferrari V, Insel PA, Junger WG (2009) Autocrine regulation of T-cell activation by ATP release and P2X7 receptors. FASEB J 23:1685–1693PubMedGoogle Scholar
  63. 63.
    Tsukimoto M, Tokunaga A, Harada H, Kojima S (2009) Blockade of murine T cell activation by antagonists of P2Y6 and P2X7 receptors. Biochem Biophys Res Commun 384:512–518PubMedGoogle Scholar
  64. 64.
    Gatof D, Kilic G, Fitz JG (2004) Vesicular exocytosis contributes to volume-sensitive ATP release in biliary cells. Am J Physiol Gastrointest Liver Physiol 286:G538–G546PubMedGoogle Scholar
  65. 65.
    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 286:25363–25376PubMedGoogle Scholar
  66. 66.
    Coco S, Calegari F, Pravettoni E, Pozzi D, Taverna E, Rosa P, Matteoli M, Verderio C (2003) Storage and release of ATP from astrocytes in culture. J Biol Chem 278:1354–1362PubMedGoogle Scholar
  67. 67.
    Pangrsic T, Potokar M, Stenovec M, Kreft M, Fabbretti E, Nistri A, Pryazhnikov E, Khiroug L, Giniatullin R, Zorec R (2007) Exocytotic release of ATP from cultured astrocytes. J Biol Chem 282:28749–28758PubMedGoogle Scholar
  68. 68.
    Zhang Z, Chen G, Zhou W, Song A, Xu T, Luo Q, Wang W, Gu XS, Duan S (2007) Regulated ATP release from astrocytes through lysosome exocytosis. Nat Cell Biol 9:945–953PubMedGoogle Scholar
  69. 69.
    Pascual O, Casper KB, Kubera C, Zhang J, Revilla-Sanchez R, Sul JY, Takano H, Moss SJ, McCarthy K, Haydon PG (2005) Astrocytic purinergic signaling coordinates synaptic networks. Science 310:113–116PubMedGoogle Scholar
  70. 70.
    Gourine AV, Kasymov V, Marina N, Tang F, Figueiredo MF, Lane S, Teschemacher AG, Spyer KM, Deisseroth K, Kasparov S (2010) Astrocytes control breathing through pH-dependent release of ATP. Science 329:571–575PubMedGoogle Scholar
  71. 71.
    Feranchak AP, Lewis MA, Kresge C, Sathe M, Bugde A, Luby-Phelps K, Antich PP, Fitz JG (2010) Initiation of purinergic signaling by exocytosis of ATP-containing vesicles in liver epithelium. J Biol Chem 285:8138–8147PubMedGoogle Scholar
  72. 72.
    Dolovcak S, Waldrop SL, Fitz JG, Kilic G (2009) 5-Nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) stimulates cellular ATP release through exocytosis of ATP-enriched vesicles. J Biol Chem 284:33894–33903PubMedGoogle Scholar
  73. 73.
    Boudreault F, Grygorczyk R (2004) Cell swelling-induced ATP release is tightly dependent on intracellular calcium elevations. J Physiol 561:499–513PubMedGoogle Scholar
  74. 74.
    Groulx N, Boudreault F, Orlov SN, Grygorczyk R (2006) Membrane reserves and hypotonic cell swelling. J Membr Biol 214:43–56PubMedGoogle Scholar
  75. 75.
    Tatur S, Groulx N, Orlov SN, Grygorczyk R (2007) Ca2+-dependent ATP release from A549 cells involves synergistic autocrine stimulation by coreleased uridine nucleotides. J Physiol 584:419–435PubMedGoogle Scholar
  76. 76.
    van der Wijk T, Tomassen SF, Houtsmuller AB, de Jonge HR, Tilly BC (2003) Increased vesicle recycling in response to osmotic cell swelling. Cause and consequence of hypotonicity-provoked ATP release. J Biol Chem 278:40020–40025PubMedGoogle Scholar
  77. 77.
    Akopova I, Tatur S, Grygorczyk M, Luchowski R, Gryczynski I, Gryczynski Z, Borejdo J, Grygorczyk R (2012) Imaging exocytosis of ATP-containing vesicles with TIRF 1 microscopy in lung epithelial A549 cells. Purinergic Signal 8:59–70PubMedGoogle Scholar
  78. 78.
    Orriss IR, Knight GE, Utting JC, Taylor SE, Burnstock G, Arnett TR (2009) Hypoxia stimulates vesicular ATP release from rat osteoblasts. J Cell Physiol 220:155–162PubMedGoogle Scholar
  79. 79.
    Chambers JK, Macdonald LE, Sarau HM, Ames RS, Freeman K, Foley JJ, Zhu Y, McLaughlin MM, Murdock P, McMillan L, Trill J, Swift A, Aiyar N, Taylor P, Vawter L, Naheed S, Szekeres P, Hervieu G, Scott C, Watson JM, Murphy AJ, Duzic E, Klein C, Bergsma DJ, Wilson S, Livi GP (2000) A G protein-coupled receptor for UDP-glucose. J Biol Chem 275:10767–10771PubMedGoogle Scholar
  80. 80.
    Moore DJ, Murdock PR, Watson JM, Faull RL, Waldvogel HJ, Szekeres PG, Wilson S, Freeman KB, Emson PC (2003) GPR105, a novel Gi/o-coupled UDP-glucose receptor expressed on brain glia and peripheral immune cells, is regulated by immunologic challenge: possible role in neuroimmune function. Brain Res Mol Brain Res 118:10–23PubMedGoogle Scholar
  81. 81.
    Scrivens M, Dickenson JM (2006) Functional expression of the P2Y(14) receptor in human neutrophils. Eur J Pharmacol 543:166–173PubMedGoogle Scholar
  82. 82.
    Gao ZG, Ding Y, Jacobson KA (2010) UDP-glucose acting at P2Y14 receptors is a mediator of mast cell degranulation. Biochem Pharmacol 79:873–879PubMedGoogle Scholar
  83. 83.
    Sesma JI, Lazarowski ER, Harden TK (2011) UDP-glucose promotes Rho activation in human neutrophils. FASEB J 25:751.16 (Abstr.)Google Scholar
  84. 84.
    Lazarowski ER, Shea DA, Boucher RC, Harden TK (2003) Release of cellular UDP-glucose as a potential extracellular signaling molecule. Mol Pharmacol 63:1190–1197PubMedGoogle Scholar
  85. 85.
    Kreda SM, Seminario-Vidal L, Heusden C, Lazarowski ER (2008) Thrombin-promoted release of UDP-glucose from human astrocytoma cells. Br J Pharmacol 153:1528–1537PubMedGoogle Scholar
  86. 86.
    Sesma JI, Esther CR Jr, Kreda SM, Jones L, O'Neal W, Nishihara S, Nicholas RA, Lazarowski ER (2009) ER/golgi nucelotide sugar transporters contribute to the cellular release of UDP-sugar signaling molecules. J Biol Chem 284:12572–12583PubMedGoogle Scholar
  87. 87.
    Ishida N, Kawakita M (2004) Molecular physiology and pathology of the nucleotide sugar transporter family (SLC35). Pflugers Arch 447:768–775PubMedGoogle Scholar
  88. 88.
    Guillen E, Hirschberg CB (1995) Transport of adenosine triphosphate into endoplasmic reticulum proteoliposomes. Biochemistry 34:5472–5476PubMedGoogle Scholar
  89. 89.
    Hirschberg CB, Robbins PW, Abeijon C (1998) Transporters of nucleotide sugars, ATP, and nucleotide sulfate in the endoplasmic reticulum and Golgi apparatus. Annu Rev Biochem 67:49–69PubMedGoogle Scholar
  90. 90.
    Schwiebert EM (1999) ABC transporter-facilitated ATP conductive transport. Am J Physiol 276:C1–C8PubMedGoogle Scholar
  91. 91.
    Roman RM, Lomri N, Braunstein G, Feranchak AP, Simeoni LA, Davison AK, Mechetner E, Schwiebert EM, Fitz JG (2001) Evidence for multidrug resistance-1 P-glycoprotein-dependent regulation of cellular ATP permeability. J Membr Biol 183:165–173PubMedGoogle Scholar
  92. 92.
    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 271:1876–1879PubMedGoogle Scholar
  93. 93.
    Grygorczyk R, Tabcharani JA, Hanrahan JW (1996) CFTR channels expressed in CHO cells do not have detectable ATP conductance. J Membr Biol 151:139–148PubMedGoogle Scholar
  94. 94.
    Watt WC, Lazarowski ER, Boucher RC (1998) Cystic fibrosis transmembrane regulator-independent release of ATP—its implications for the regulation of P2Y(2) receptors in airway epithelia. J Biol Chem 273:14053–14058PubMedGoogle Scholar
  95. 95.
    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 281:22992–23002PubMedGoogle Scholar
  96. 96.
    Okada SF, O'Neal WK, Huang P, Nicholas RA, Ostrowski LE, Craigen WJ, Lazarowski ER, Boucher RC (2004) Voltage-dependent anion channel-1 (VDAC-1) contributes to ATP release and cell volume regulation in murine cells. J Gen Physiol 124:513–526PubMedGoogle Scholar
  97. 97.
    Sabirov R, Okada Y (2005) ATP release via anion channels. Purinergic Signal 1:311–328PubMedGoogle Scholar
  98. 98.
    Sabirov RZ, Okada Y (2009) The maxi-anion channel: a classical channel playing novel roles through an unidentified molecular entity. J Physiol Sci 59:3–21PubMedGoogle Scholar
  99. 99.
    Sabirov RZ, Dutta AK, Okada Y (2001) Volume-dependent ATP-conductive large-conductance anion channel as a pathway for swelling-induced ATP release. J Gen Physiol 118:251–266PubMedGoogle Scholar
  100. 100.
    Sabirov RZ, Okada Y (2004) Wide nanoscopic pore of maxi-anion channel suits its function as an ATP-conductive pathway. Biophys J 87:1672–1685PubMedGoogle Scholar
  101. 101.
    Nilius B, Droogmans G (2003) Amazing chloride channels: an overview. Acta Physiol Scand 177:119–147PubMedGoogle Scholar
  102. 102.
    Hisadome K, Koyama T, Kimura C, Droogmans G, Ito Y, Oike M (2002) Volume-regulated anion channels serve as an auto/paracrine nucleotide release pathway in aortic endothelial cells. J Gen Physiol 119:511–520PubMedGoogle Scholar
  103. 103.
    Okada Y (1997) Volume expansion-sensing outward-rectifier Cl- channel: fresh start to the molecular identity and volume sensor. Am J Physiol 273:C755–C789PubMedGoogle Scholar
  104. 104.
    Okada Y, Sato K, Numata T (2009) Pathophysiology and puzzles of the volume-sensitive outwardly rectifying anion channel. J Physiol 587:2141–2149PubMedGoogle Scholar
  105. 105.
    Blum AE, Walsh BC, Dubyak GR (2010) Extracellular osmolarity modulates G protein-coupled receptor-dependent ATP release from 1321N1 astrocytoma cells. Am J Physiol Cell Physiol 298:C386–C396PubMedGoogle Scholar
  106. 106.
    Hazama A, Shimizu T, Ando-Akatsuka Y, Hayashi S, Tanaka S, Maeno E, Okada Y (1999) Swelling-induced, CFTR-independent ATP release from a human epithelial cell line. J Gen Physiol 114:525–533PubMedGoogle Scholar
  107. 107.
    Liu HT, Akita T, Shimizu T, Sabirov RZ, Okada Y (2009) Bradykinin-induced astrocyte-neuron signalling: glutamate release is mediated by ROS-activated volume-sensitive outwardly rectifying anion channels. J Physiol 587:2197–2209PubMedGoogle Scholar
  108. 108.
    Suzuki M, Mizuno A (2004) A novel human Cl(−) channel family related to Drosophila flightless locus. J Biol Chem 279:22461–22468PubMedGoogle Scholar
  109. 109.
    Chen Y, Yao Y, Sumi Y, Li A, To UK, Elkhal A, Inoue Y, Woehrle T, Zhang Q, Hauser C, Junger WG (2010) Purinergic signaling: a fundamental mechanism in neutrophil activation. Sci Signal 3:ra45PubMedGoogle Scholar
  110. 110.
    Scemes E, Spray DC, Meda P (2009) Connexins, pannexins, innexins: novel roles of “hemi-channels”. Pflugers Arch 457:1207–1226PubMedGoogle Scholar
  111. 111.
    D'hondt C, Ponsaerts R, De SH, Vinken M, De VE, De BM, Wang N, Rogiers V, Leybaert L, Himpens B, Bultynck G (2011) Pannexin channels in ATP release and beyond: an unexpected rendezvous at the endoplasmic reticulum. Cell Signal 23:305–316PubMedGoogle Scholar
  112. 112.
    Thompson RJ, MacVicar BA (2008) Connexin and pannexin hemichannels of neurons and astrocytes. Channels (Austin) 2:81–86Google Scholar
  113. 113.
    D'hondt C, Ponsaerts R, De SH, Bultynck G, Himpens B (2009) Pannexins, distant relatives of the connexin family with specific cellular functions? BioEssays 31:953–974PubMedGoogle Scholar
  114. 114.
    Nakagawa S, Maeda S, Tsukihara T (2010) Structural and functional studies of gap junction channels. Curr Opin Struct Biol 20:423–430PubMedGoogle Scholar
  115. 115.
    Wang J, Ma M, Locovei S, Keane RW, Dahl G (2007) Modulation of membrane channel currents by gap junction protein mimetic peptides: size matters. Am J Physiol Cell Physiol 293:C1112–C1119PubMedGoogle Scholar
  116. 116.
    Muller DJ, Hand GM, Engel A, Sosinsky GE (2002) Conformational changes in surface structures of isolated connexin 26 gap junctions. EMBO J 21:3598–3607PubMedGoogle Scholar
  117. 117.
    Cotrina ML, Lin JH, Alves-Rodrigues A, Liu S, Li J, Azmi-Ghadimi H, Kang J, Naus CC, Nedergaard M (1998) Connexins regulate calcium signaling by controlling ATP release. Proc Natl Acad Sci U S A 95:15735–15740PubMedGoogle Scholar
  118. 118.
    Arcuino G, Lin JH, Takano T, Liu C, Jiang L, Gao Q, Kang J, Nedergaard M (2002) Intercellular calcium signaling mediated by point-source burst release of ATP. Proc Natl Acad Sci U S A 99:9840–9845PubMedGoogle Scholar
  119. 119.
    Kang J, Kang N, Lovatt D, Torres A, Zhao Z, Lin J, Nedergaard M (2008) Connexin 43 hemichannels are permeable to ATP. J Neurosci 28:4702–4711PubMedGoogle Scholar
  120. 120.
    Romanello M, Pani B, Bicego M, D'Andrea P (2001) Mechanically induced ATP release from human osteoblastic cells. Biochem Biophys Res Commun 289:1275–1281PubMedGoogle Scholar
  121. 121.
    De Vuyst E, Decrock E, Cabooter L, Dubyak GR, Naus CC, Evans WH, Leybaert L (2005) Intracellular calcium changes trigger connexin 32 hemichannel opening. EMBO J 25:34–44PubMedGoogle Scholar
  122. 122.
    De Vuyst E, Wang N, Decrock E, De Bock M, Vinken M, Van Moorhem M, Lai C, Culot M, Rogiers V, Cecchelli R, Naus CC, Evans WH, Leybaert L (2009) Ca(2+) regulation of connexin 43 hemichannels in C6 glioma and glial cells. Cell Calcium 46:176–187PubMedGoogle Scholar
  123. 123.
    Toma I, Bansal E, Meer EJ, Kang JJ, Vargas SL, Peti-Peterdi J (2008) Connexin 40 and ATP-dependent intercellular calcium wave in renal glomerular endothelial cells. Am J Physiol Regul Integr Comp Physiol 294:R1769–R1776PubMedGoogle Scholar
  124. 124.
    Schock SC, Leblanc D, Hakim AM, Thompson CS (2008) ATP release by way of connexin 36 hemichannels mediates ischemic tolerance in vitro. Biochem Biophys Res Commun 368:138–144PubMedGoogle Scholar
  125. 125.
    Huckstepp RT, Id BR, Eason R, Spyer KM, Dicke N, Willecke K, Marina N, Gourine AV, Dale N (2010) Connexin hemichannel-mediated CO2-dependent release of ATP in the medulla oblongata contributes to central respiratory chemosensitivity. J Physiol 588:3901–3920PubMedGoogle Scholar
  126. 126.
    Funk GD (2010) The ‘connexin’ between astrocytes, ATP and central respiratory chemoreception. J Physiol 588:4335–4337PubMedGoogle Scholar
  127. 127.
    Dale N, Frenguelli BG (2009) Release of adenosine and ATP during ischemia and epilepsy. Curr Neuropharmacol 7:160–179PubMedGoogle Scholar
  128. 128.
    Anselmi F, Hernandez VH, Crispino G, Seydel A, Ortolano S, Roper SD, Kessaris N, Richardson W, Rickheit G, Filippov MA, Monyer H, Mammano F (2008) ATP release through connexin hemichannels and gap junction transfer of second messengers propagate Ca2+ signals across the inner ear. Proc Natl Acad Sci U S A 105:18770–18775PubMedGoogle Scholar
  129. 129.
    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 20:1724–1732PubMedGoogle Scholar
  130. 130.
    Mironova E, Peti-Peterdi J, Bugaj V, Stockand JD (2011) Diminished paracrine regulation of the epithelial Na+ channel by purinergic signaling in mice lacking connexin 30. J Biol Chem 286:1054–1060PubMedGoogle Scholar
  131. 131.
    Eltzschig HK, Macmanus CF, Colgan SP (2008) Neutrophils as sources of extracellular nucleotides: functional consequences at the vascular interface. Trends Cardiovasc Med 18:103–107PubMedGoogle Scholar
  132. 132.
    Eltzschig HK, Eckle T, Mager A, Kuper N, Karcher C, Weissmuller T, Boengler K, Schulz R, Robson SC, Colgan SP (2006) ATP release from activated neutrophils occurs via connexin 43 and modulates adenosine-dependent endothelial cell function. Circ Res 99:1100–1108PubMedGoogle Scholar
  133. 133.
    Chen Y, Corriden R, Inoue Y, Yip L, Hashiguchi N, Zinkernagel A, Nizet V, Insel PA, Junger WG (2006) ATP release guides neutrophil chemotaxis via P2Y2 and A3 receptors. Science 314:1792–1795PubMedGoogle Scholar
  134. 134.
    Toyofuku T, Yabuki M, Otsu K, Kuzuya T, Hori M, Tada M (1998) Direct association of the gap junction protein connexin-43 with ZO-1 in cardiac myocytes. J Biol Chem 273:12725–12731PubMedGoogle Scholar
  135. 135.
    Singh D, Lampe PD (2003) Identification of connexin-43 interacting proteins. Cell Commun Adhes 10:215–220PubMedGoogle Scholar
  136. 136.
    Gilleron J, Fiorini C, Carette D, Avondet C, Falk MM, Segretain D, Pointis G (2008) Molecular reorganization of Cx43, Zo-1 and Src complexes during the endocytosis of gap junction plaques in response to a non-genomic carcinogen. J Cell Sci 121:4069–4078PubMedGoogle Scholar
  137. 137.
    Langlois S, Cowan KN, Shao Q, Cowan BJ, Laird DW (2010) The tumor-suppressive function of Connexin43 in keratinocytes is mediated in part via interaction with caveolin-1. Cancer Res 70:4222–4232PubMedGoogle Scholar
  138. 138.
    Scemes E (2008) Modulation of astrocyte P2Y1 receptors by the carboxyl terminal domain of the gap junction protein Cx43. Glia 56:145–153PubMedGoogle Scholar
  139. 139.
    Spray DC, Iacobas DA (2007) Organizational principles of the connexin-related brain transcriptome. J Membr Biol 218:39–47PubMedGoogle Scholar
  140. 140.
    Iacobas DA, Iacobas S, Urban-Maldonado M, Scemes E, Spray DC (2008) Similar transcriptomic alterations in Cx43 knockdown and knockout astrocytes. Cell Commun Adhes 15:195–206PubMedGoogle Scholar
  141. 141.
    Ambrosi C, Gassmann O, Pranskevich JN, Boassa D, Smock A, Wang J, Dahl G, Steinem C, Sosinsky GE (2010) Pannexin1 and Pannexin2 channels show quaternary similarities to connexons and different oligomerization numbers from each other. J Biol Chem 285:24420–24431PubMedGoogle Scholar
  142. 142.
    Penuela S, Bhalla R, Gong XQ, Cowan KN, Celetti SJ, Cowan BJ, Bai D, Shao Q, Laird DW (2007) Pannexin 1 and pannexin 3 are glycoproteins that exhibit many distinct characteristics from the connexin family of gap junction proteins. J Cell Sci 120:3772–3783PubMedGoogle Scholar
  143. 143.
    Boassa D, Qiu F, Dahl G, Sosinsky G (2008) Trafficking dynamics of glycosylated pannexin 1 proteins. Cell Commun Adhes 15:119–132PubMedGoogle Scholar
  144. 144.
    Bruzzone R, Barbe MT, Jakob NJ, Monyer H (2005) Pharmacological properties of homomeric and heteromeric pannexin hemichannels expressed in Xenopus oocytes. J Neurochem 92:1033–1043PubMedGoogle Scholar
  145. 145.
    Dahl G, Locovei S (2006) Pannexin: to gap or not to gap, is that a question? IUBMB Life 58:409–419PubMedGoogle Scholar
  146. 146.
    Ma W, Hui H, Pelegrin P, Surprenant A (2009) Pharmacological characterization of pannexin-1 currents expressed in mammalian cells. J Pharmacol Exp Ther 328:409–418PubMedGoogle Scholar
  147. 147.
    Silverman W, Locovei S, Dahl G (2008) Probenecid, a gout remedy, inhibits pannexin 1 channels. Am J Physiol Cell Physiol 295:C761–C767PubMedGoogle Scholar
  148. 148.
    Pelegrin P, Surprenant A (2006) Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. EMBO J 25:5071–5082PubMedGoogle Scholar
  149. 149.
    Bao L, Locovei S, Dahl G (2004) Pannexin membrane channels are mechanosensitive conduits for ATP. FEBS Lett 572:65–68PubMedGoogle Scholar
  150. 150.
    Locovei S, Bao L, Dahl G (2006) Pannexin 1 in erythrocytes: function without a gap. Proc Natl Acad Sci U S A 103:7655–7659PubMedGoogle Scholar
  151. 151.
    Ransford GA, Fregien N, Qiu F, Dahl G, Conner GE, Salathe M (2009) Pannexin 1 contributes to ATP release in airway epithelia. Am J Respir Cell Mol Biol 41:525–534PubMedGoogle Scholar
  152. 152.
    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 286:26277–26286PubMedGoogle Scholar
  153. 153.
    Seminario-Vidal L, Kreda S, Jones L, O'Neal W, Trejo J, Boucher RC, Lazarowski ER (2009) Thrombin promotes release of ATP from lung epithelial cells through coordinated activation of Rho- and Ca2+-dependent signaling pathways. J Biol Chem 284:20638–20648PubMedGoogle Scholar
  154. 154.
    Sridharan M, Adderley SP, Bowles EA, Egan TM, Stephenson AH, Ellsworth ML, Sprague RS (2010) Pannexin 1 is the conduit for low oxygen tension-induced atp release from human erythrocytes. Am J Physiol Heart Circ Physiol 299:H1146–H1152PubMedGoogle Scholar
  155. 155.
    Zhu H, Zennadi R, Xu BX, Eu JP, Torok JA, Telen MJ, McMahon TJ (2011) Impaired adenosine-5′-triphosphate release from red blood cells promotes their adhesion to endothelial cells: a mechanism of hypoxemia after transfusion. Crit Care Med 39:2478–2486PubMedGoogle Scholar
  156. 156.
    Forsyth AM, Wan J, Owrutsky PD, Abkarian M, Stone HA (2011) Multiscale approach to link red blood cell dynamics, shear viscosity, and ATP release. Proc Natl Acad Sci U S A 108:10986–10991PubMedGoogle Scholar
  157. 157.
    Li A, Leung CT, Peterson-Yantorno K, Mitchell CH, Civan MM (2010) Pathways for ATP release by bovine ciliary epithelial cells, the initial step in purinergic regulation of aqueous humor inflow. Am J Physiol Cell Physiol 299:C1308–C1317PubMedGoogle Scholar
  158. 158.
    Reigada D, Lu W, Zhang M, Mitchell CH (2008) Elevated pressure triggers a physiological release of ATP from the retina: possible role for pannexin hemichannels. Neuroscience 157:396–404PubMedGoogle Scholar
  159. 159.
    Li A, Leung CT, Peterson-Yantorno K, Stamer WD, Mitchell CH, Civan MM (2011) Mechanisms of ATP release by human trabecular meshwork cells, the enabling step in purinergic regulation of aqueous humor outflow. J Cell Physiol (in press)Google Scholar
  160. 160.
    Buvinic S, Almarza G, Bustamante M, Casas M, Lopez J, Riquelme M, Saez JC, Huidobro-Toro JP, Jaimovich E (2009) ATP released by electrical stimuli elicits calcium transients and gene expression in skeletal muscle. J Biol Chem 284:34490–34505PubMedGoogle Scholar
  161. 161.
    Huang YJ, Maruyama Y, Dvoryanchikov G, Pereira E, Chaudhari N, Roper SD (2007) The role of pannexin 1 hemichannels in ATP release and cell–cell communication in mouse taste buds. Proc Natl Acad Sci U S A 104:6436–6441PubMedGoogle Scholar
  162. 162.
    Chekeni FB, Elliott MR, Sandilos JK, Walk SF, Kinchen JM, Lazarowski ER, Armstrong AJ, Penuela S, Laird DW, Salvesen GS, Isakson BE, Bayliss DA, Ravichandran KS (2010) Pannexin 1 channels mediate ‘find-me’ signal release and membrane permeability during apoptosis. Nature 467:863–867PubMedGoogle Scholar
  163. 163.
    Nishida M, Sato Y, Uemura A, Narita Y, Tozaki-Saitoh H, Nakaya M, Ide T, Suzuki K, Inoue K, Nagao T, Kurose H (2008) P2Y6 receptor-Galpha12/13 signalling in cardiomyocytes triggers pressure overload-induced cardiac fibrosis. EMBO J 27:3104–3115PubMedGoogle Scholar
  164. 164.
    Seror C, Melki MT, Subra F, Raza SQ, Bras M, Saidi H, Nardacci R, Voisin L, Paoletti A, Law F, Martins I, Amendola A, Abdul-Sater AA, Ciccosanti F, Delelis O, Niedergang F, Thierry S, Said-Sadier N, Lamaze C, Metivier D, Estaquier J, Fimia GM, Falasca L, Casetti R, Modjtahedi N, Kanellopoulos J, Mouscadet JF, Ojcius DM, Piacentini M, Gougeon ML, Kroemer G, Perfettini JL (2011) Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection. J Exp Med 208:1823–1834PubMedGoogle Scholar
  165. 165.
    Iglesias R, Dahl G, Qiu F, Spray DC, Scemes E (2009) Pannexin 1: the molecular substrate of astrocyte “hemichannels”. J Neurosci 29:7092–7097PubMedGoogle Scholar
  166. 166.
    Billaud M, Lohman AW, Straub AC, Looft-Wilson R, Johnstone SR, Araj CA, Best AK, Chekeni FB, Ravichandran KS, Penuela S, Laird DW, Isakson BE (2011) Pannexin1 regulates {alpha}1-adrenergic receptor-mediated vasoconstriction. Circ Res 109:80–85PubMedGoogle Scholar
  167. 167.
    Qiu F, Wang J, Spray DC, Scemes E, Dahl G (2011) Two non-vesicular ATP release pathways in the mouse erythrocyte membrane. FEBS Lett 585:3430–3435PubMedGoogle Scholar
  168. 168.
    Elliott MR, Chekeni FB, Trampont PC, Lazarowski ER, Kadl A, Walk SF, Park D, Woodson RI, Ostankovich M, Sharma P, Lysiak JJ, Harden TK, Leitinger N, Ravichandran KS (2009) Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 461:282–286PubMedGoogle Scholar
  169. 169.
    Qu Y, Misaghi S, Newton K, Gilmour LL, Louie S, Cupp JE, Dubyak GR, Hackos D, Dixit VM (2011) Pannexin-1 is required for ATP release during apoptosis but not for inflammasome activation. J Immunol 186:6553–6561PubMedGoogle Scholar
  170. 170.
    Locovei S, Wang J, Dahl G (2006) Activation of pannexin 1 channels by ATP through P2Y receptors and by cytoplasmic calcium. FEBS Lett 580:239–244PubMedGoogle Scholar
  171. 171.
    Kienitz MC, Bender K, Dermietzel R, Pott L, Zoidl G (2011) Pannexin 1 constitutes the large conductance cation channel of cardiac myocytes. J Biol Chem 286:290–298PubMedGoogle Scholar
  172. 172.
    Qiu F, Dahl G (2009) A permeant regulating its permeation pore: inhibition of pannexin 1 channels by ATP. Am J Physiol Cell Physiol 296:C250–C255PubMedGoogle Scholar
  173. 173.
    Bunse S, Locovei S, Schmidt M, Qiu F, Zoidl G, Dahl G, Dermietzel R (2009) The potassium channel subunit Kvbeta3 interacts with pannexin 1 and attenuates its sensitivity to changes in redox potentials. FEBS J 276:6258–6270PubMedGoogle Scholar
  174. 174.
    Bunse S, Schmidt M, Prochnow N, Zoidl G, Dermietzel R (2010) Intracellular cysteine 346 is essentially involved in regulating Panx1 channel activity. J Biol Chem 285:38444–38452PubMedGoogle Scholar
  175. 175.
    Bhalla-Gehi R, Penuela S, Churko JM, Shao Q, Laird DW (2010) Pannexin1 and pannexin3 delivery, cell surface dynamics, and cytoskeletal interactions. J Biol Chem 285:9147–9160PubMedGoogle Scholar
  176. 176.
    Thompson RJ, Zhou N, MacVicar BA (2006) Ischemia opens neuronal gap junction hemichannels. Science 312:924–927PubMedGoogle Scholar
  177. 177.
    Thompson RJ, Jackson MF, Olah ME, Rungta RL, Hines DJ, Beazely MA, MacDonald JF, MacVicar BA (2008) Activation of pannexin-1 hemichannels augments aberrant bursting in the hippocampus. Science 322:1555–1559PubMedGoogle Scholar
  178. 178.
    Locovei S, Scemes E, Qiu F, Spray DC, Dahl G (2007) Pannexin1 is part of the pore forming unit of the P2X(7) receptor death complex. FEBS Lett 581:483–488PubMedGoogle Scholar
  179. 179.
    Penuela S, Celetti SJ, Bhalla R, Shao Q, Laird DW (2008) Diverse subcellular distribution profiles of pannexin 1 and pannexin 3. Cell Commun Adhes 15:133–142PubMedGoogle Scholar
  180. 180.
    Iwamoto T, Nakamura T, Doyle A, Ishikawa M, de Vega S, Fukumoto S, Yamada Y (2010) Pannexin 3 regulates intracellular ATP/cAMP levels and promotes chondrocyte differentiation. J Biol Chem 285:18948–18958PubMedGoogle Scholar
  181. 181.
    Ishikawa M, Iwamoto T, Nakamura T, Doyle A, Fukumoto S, Yamada Y (2011) Pannexin 3 functions as an ER Ca(2+) channel, hemichannel, and gap junction to promote osteoblast differentiation. J Cell Biol 193:1257–1274PubMedGoogle Scholar
  182. 182.
    Virginio C, MacKenzie A, Rassendren FA, North RA, Surprenant A (1999) Pore dilation of neuronal P2X receptor channels. Nat Neurosci 2:315–321PubMedGoogle Scholar
  183. 183.
    Virginio C, MacKenzie A, North RA, Surprenant A (1999) Kinetics of cell lysis, dye uptake and permeability changes in cells expressing the rat P2X7 receptor. J Physiol 519(Pt 2):335–346PubMedGoogle Scholar
  184. 184.
    Pellegatti P, Falzoni S, Pinton P, Rizzuto R, Di Virgilio F (2005) A novel recombinant plasma membrane-targeted luciferase reveals a new pathway for ATP secretion. Mol Biol Cell 16:3659–3665PubMedGoogle Scholar
  185. 185.
    Suadicani SO, Brosnan CF, Scemes E (2006) P2X7 receptors mediate ATP release and amplification of astrocytic intercellular Ca2+ signaling. J Neurosci 26:1378–1385PubMedGoogle Scholar
  186. 186.
    Venkatachalam K, Montell C (2007) TRP channels. Annu Rev Biochem 76:387–417PubMedGoogle Scholar
  187. 187.
    O'Neil RG, Heller S (2005) The mechanosensitive nature of TRPV channels. Pflugers Arch 451:193–203PubMedGoogle Scholar
  188. 188.
    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–F1713PubMedGoogle Scholar
  189. 189.
    Mochizuki T, Sokabe T, Araki I, Fujishita K, Shibasaki K, Uchida K, Naruse K, Koizumi S, Takeda M, Tominaga M (2009) The TRPV4 cation channel mediates stretch-evoked Ca2+ influx and ATP release in primary urothelial cell cultures. J Biol Chem 284:21257–21264PubMedGoogle Scholar
  190. 190.
    Gevaert T, Vriens J, Segal A, Everaerts W, Roskams T, Talavera K, Owsianik G, Liedtke W, Daelemans D, Dewachter I, Van Leuven F, Voets T, De Ridder D, Nilius B (2007) Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding. J Clin Invest 117:3453–3462PubMedGoogle Scholar
  191. 191.
    Silva GB, Garvin JL (2008) TRPV4 mediates hypotonicity-induced ATP release by the thick ascending limb. Am J Physiol Renal Physiol 295:F1090–F1095PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.School of MedicineUniversity of North CarolinaChapel HillUSA
  2. 2.Cystic Fibrosis/Pulmonary Research & Treatment CenterUniversity of North CarolinaChapel HillUSA

Personalised recommendations