Skip to main content
SpringerLink
Log in

The ecto-enzymes CD73 and adenosine deaminase modulate 5′-AMP-derived adenosine in myofibroblasts of the rat small intestine

  • Original Article
  • Published:
Purinergic Signalling Aims and scope Submit manuscript

Abstract

Adenosine is a versatile signaling molecule recognized to physiologically influence gut motor functions. Both the duration and magnitude of adenosine signaling in enteric neuromuscular function depend on its availability, which is regulated by the ecto-enzymes ecto-5′-nucleotidase (CD73), alkaline phosphatase (AP), and ecto-adenosine deaminase (ADA) and by dipyridamole-sensitive equilibrative transporters (ENTs). Our purpose was to assess the involvement of CD73, APs, ecto-ADA in the formation of AMP-derived adenosine in primary cultures of ileal myofibroblasts (IMFs). IMFs were isolated from rat ileum longitudinal muscle segments by means of primary explant technique and identified by immunofluorescence staining for vimentin and α-smooth muscle actin. IMFs confluent monolayers were exposed to exogenous 5′-AMP in the presence or absence of CD73, APs, ecto-ADA, or ENTs inhibitors. The formation of adenosine and its metabolites in the IMFs medium was monitored by high-performance liquid chromatography. The distribution of CD73 and ADA in IMFs was detected by confocal immunocytochemistry and qRT-PCR. Exogenous 5′-AMP was rapidly cleared being almost undetectable after 60-min incubation, while adenosine levels significantly increased. Treatment of IMFs with CD73 inhibitors markedly reduced 5′-AMP clearance whereas ADA blockade or inhibition of both ADA and ENTs prevented adenosine catabolism. By contrast, inhibition of APs did not affect 5′-AMP metabolism. Immunofluorescence staining and qRT-PCR analysis confirmed the expression of CD73 and ADA in IMFs. Overall, our data show that in IMFs an extracellular AMP-adenosine pathway is functionally active and among the different enzymatic pathways regulating extracellular adenosine levels, CD73 and ecto-ADA represent the critical catabolic pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Abbreviations

ADA:

Adenosine deaminase

AOPCP:

α,β-methyleneadenosine 5′-diphosphate sodium salt

CD73:

ecto-5′-nucleotidase

EHNA:

Erythro-9-(2-hydroxy-3-nonyl) adenine

ENTs:

Equilibrative transporters

HPLC:

High-pressure liquid chromatography

IMFs:

Ileal myofibroblasts

AP:

Alkaline phosphatase

PAP:

Prostatic acid phosphatase

References

  1. Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50:413–492

    CAS  PubMed  Google Scholar 

  2. Christofi FL, Zhang H, Yu JG, Guzman J, Xue J, Kim M, Wang YZ, Cooke HJ (2001) Differential gene expression of adenosine A1, A2a, A2b, and A3 receptors in the human enteric nervous system. J Comp Neurol 439:46–64

    Article  CAS  Google Scholar 

  3. Kolachala VL, Bajaj R, Chalasani M, Sitaraman SV (2008) Purinergic receptors in gastrointestinal inflammation. Am J Physiol Gastrointest Liver Physiol 294(2):G401–G410. https://doi.org/10.1152/ajpgi.00454.2007

    Article  CAS  PubMed  Google Scholar 

  4. Antonioli L, Colucci R, Pellegrini C, Giustarini G, Tuccori M, Blandizzi C, Fornai M (2013) The role of purinergic pathways in the pathophysiology of gut diseases: pharmacological modulation and potential therapeutic applications. Pharmacol Ther 139(2):157–188. https://doi.org/10.1016/j.pharmthera.2013.04.002

    Article  CAS  PubMed  Google Scholar 

  5. Zoppellaro C, Bin A, Brun P, Banzato S, Macchi V, Castagliuolo I, Giron MC (2013) Adenosine-mediated enteric neuromuscular function is affected during herpes simplex virus type 1 infection of rat enteric nervous system. PLoS One 8(8):e72648. https://doi.org/10.1371/journal.pone.0072648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Idzko M, Ferrari D, Eltzschig HK (2014) Nucleotide signalling during inflammation. Nature 509(7500):310–317. https://doi.org/10.1038/nature13085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Nitahara K, Kittel A, Liang SD, Vizi ES (1995) A1-receptor-mediated effect of adenosine on the release of acetylcholine from the myenteric plexus: role and localization of ecto-ATPase and 5′-nucleotidase. Neuroscience 67(1):159–168

    Article  CAS  Google Scholar 

  8. Duarte-Araujo M, Nascimento C, Alexandrina Timoteo M, Magalhaes-Cardoso T, Correia-de-Sa P (2004) Dual effects of adenosine on acetylcholine release from myenteric motoneurons are mediated by junctional facilitatory A(2A) and extrajunctional inhibitory A(1) receptors. Br J Pharmacol 141(6):925–934. https://doi.org/10.1038/sj.bjp.0705697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Correia-de-Sa P, Adaes S, Timoteo MA, Vieira C, Magalhaes-Cardoso T, Nascimento C, Duarte-Araujo M (2006) Fine-tuning modulation of myenteric motoneurons by endogenous adenosine: on the role of secreted adenosine deaminase. Autonomic neuroscience: basic & clinical 126–127:211–224. https://doi.org/10.1016/j.autneu.2006.02.004

    Article  CAS  Google Scholar 

  10. Giron MC, Bin A, Brun P, Etteri S, Bolego C, Florio C, Gaion RM (2008) Cyclic AMP in rat ileum: evidence for the presence of an extracellular cyclic AMP-adenosine pathway. Gastroenterology 134(4):1116–1126. https://doi.org/10.1053/j.gastro.2008.01.030

    Article  CAS  PubMed  Google Scholar 

  11. Fukuuchi T, Kobayashi M, Yamaoka N, Kaneko K (2016) Evaluation of cellular purine transport and metabolism in the Caco-2 cell using comprehensive high-performance liquid chromatography method for analysis of purines. Nucleosides Nucleotides Nucleic Acids 35(10–12):663–669. https://doi.org/10.1080/15257770.2016.1205195

    Article  CAS  PubMed  Google Scholar 

  12. Antonioli L, Pellegrini C, Fornai M, Tirotta E, Gentile D, Benvenuti L, Giron MC, Caputi V, Marsilio I, Orso G, Bernardini N, Segnani C, Ippolito C, Csóka B, Németh ZH, Haskó G, Scarpignato C, Blandizzi C, Colucci R (2017) Colonic motor dysfunctions in a mouse model of high-fat diet-induced obesity: an involvement of A(2B) adenosine receptors. Purinergic Signal 13(4):497–510

    Article  CAS  Google Scholar 

  13. Duarte-Araujo M, Nascimento C, Timoteo MA, Magalhaes-Cardoso MT, Correia-de-Sa P (2009) Relative contribution of ecto-ATPase and ecto-ATPDase pathways to the biphasic effect of ATP on acetylcholine release from myenteric motoneurons. Br J Pharmacol 156(3):519–533. https://doi.org/10.1111/j.1476-5381.2008.00058.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Antonioli L, Pacher P, Vizi ES, Hasko G (2013) CD39 and CD73 in immunity and inflammation. Trends Mol Med 19(6):355–367. https://doi.org/10.1016/j.molmed.2013.03.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Cardoso AM, Schetinger MR, Correia-de-Sa P, Sevigny J (2015) Impact of ectonucleotidases in autonomic nervous functions. Auton Neurosci 191:25–38. https://doi.org/10.1016/j.autneu.2015.04.014

    Article  CAS  PubMed  Google Scholar 

  16. Jackson EK, Mi Z, Dubey RK (2007) The extracellular cAMP-adenosine pathway significantly contributes to the in vivo production of adenosine. J Pharmacol Exp Ther 320(1):117–123. https://doi.org/10.1124/jpet.106.112748

    Article  CAS  PubMed  Google Scholar 

  17. Pacheco R, Martinez-Navio JM, Lejeune M, Climent N, Oliva H, Gatell JM, Gallart T, Mallol J, Lluis C, Franco R (2005) CD26, adenosine deaminase, and adenosine receptors mediate costimulatory signals in the immunological synapse. Proc Natl Acad Sci U S A 102(27):9583–9588. https://doi.org/10.1073/pnas.0501050102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Antonioli L, Colucci R, La Motta C, Tuccori M, Awwad O, Da Settimo F, Blandizzi C, Fornai M (2012) Adenosine deaminase in the modulation of immune system and its potential as a novel target for treatment of inflammatory disorders. Curr Drug Targets 13(6):842–862

    Article  CAS  Google Scholar 

  19. Vieira C, Magalhaes-Cardoso MT, Ferreirinha F, Silva I, Dias AS, Pelletier J, Sevigny J, Correia-de-Sa P (2014) Feed-forward inhibition of CD73 and upregulation of adenosine deaminase contribute to the loss of adenosine neuromodulation in postinflammatory ileitis. Mediat Inflamm 2014:254640. https://doi.org/10.1155/2014/254640

    Article  CAS  Google Scholar 

  20. Synnestvedt K, Furuta GT, Comerford KM, Louis N, Karhausen J, Eltzschig HK, Hansen KR, Thompson LF, Colgan SP (2002) Ecto-5′-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia. J Clin Investig 110(7):993–1002. https://doi.org/10.1172/jci15337

    Article  CAS  PubMed  Google Scholar 

  21. Stefanovic V, Mandel P, Rosenberg A (1975) Concanavalin A inhibition of ecto-5′-nucleotidase of intact cultured C6 glioma cells. J Biol Chem 250(17):7081–7083

    CAS  PubMed  Google Scholar 

  22. Picher M, Burch LH, Hirsh AJ, Spychala J, Boucher RC (2003) Ecto 5′-nucleotidase and nonspecific alkaline phosphatase. Two AMP-hydrolyzing ectoenzymes with distinct roles in human airways. J Biol Chem 278(15):13468–13479. https://doi.org/10.1074/jbc.M300569200

    Article  CAS  PubMed  Google Scholar 

  23. Caputi V, Marsilio I, Filpa V, Cerantola S, Orso G, Bistoletti M, Paccagnella N, De Martin S, Montopoli M, Dall'Acqua S, Crema F, Di Gangi IM, Galuppini F, Lante I, Bogialli S, Rugge M, Debetto P, Giaroni C, Giron MC (2017) Antibiotic-induced dysbiosis of the microbiota impairs gut neuromuscular function in juvenile mice. Br J Pharmacol 174(20):3623–3639

    Article  CAS  Google Scholar 

  24. Mifflin RC, Pinchuk IV, Saada JI, Powell DW (2011) Intestinal myofibroblasts: targets for stem cell therapy. Am J Physiol Gastrointest Liver Physiol 300(5):G684–G696. https://doi.org/10.1152/ajpgi.00474.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Achenbach JE, Topliff CL, Vassilev VB, Donis RO, Eskridge KM, Kelling CL (2004) Detection and quantitation of bovine respiratory syncytial virus using real-time quantitative RT-PCR and quantitative competitive RT-PCR assays. J Virol Methods 121(1):1–6. https://doi.org/10.1016/j.jviromet.2004.05.004

    Article  CAS  PubMed  Google Scholar 

  26. Qin X, Liu S, Lu Q, Zhang M, Jiang X, Hu S, Li J, Zhang C, Gao J, Zhu MS, Feil R, Li H, Chen M, Weinstein LS, Zhang Y, Zhang W (2017) Heterotrimeric G stimulatory protein alpha subunit is required for intestinal smooth muscle contraction in mice. Gastroenterology 152(5):1114–1125.e1115. https://doi.org/10.1053/j.gastro.2016.12.017

    Article  CAS  PubMed  Google Scholar 

  27. Brun P, Giron MC, Zoppellaro C, Bin A, Porzionato A, De Caro R, Barbara G, Stanghellini V, Corinaldesi R, Zaninotto G, Palù G, Gaion RM, Tonini M, De Giorgio R, Castagliuolo I (2010) Herpes simplex virus type 1 infection of the rat enteric nervous system evokes small-bowel neuromuscular abnormalities. Gastroenterology 138(5):1790–1801. https://doi.org/10.1053/j.gastro.2010.01.036

    Article  CAS  PubMed  Google Scholar 

  28. Chen W, Lu C, Hirota C, Iacucci M, Ghosh S, Gui X (2017) Smooth muscle hyperplasia/hypertrophy is the most prominent histological change in Crohn’s fibrostenosing bowel strictures: a semiquantitative analysis by using a novel histological grading scheme. J Crohn’s Colitis 11(1):92–104. https://doi.org/10.1093/ecco-jcc/jjw126

    Article  Google Scholar 

  29. Longhi MS, Moss A, Jiang ZG, Robson SC (2017) Purinergic signaling during intestinal inflammation. J Mol Med (Berlin, Germany) 95(9):915–925. https://doi.org/10.1007/s00109-017-1545-1

    Article  CAS  Google Scholar 

  30. Severi C, Sferra R, Scirocco A, Vetuschi A, Pallotta N, Pronio A, Caronna R, Di Rocco G, Gaudio E, Corazziari E, Onori P (2014) Contribution of intestinal smooth muscle to Crohn’s disease fibrogenesis. Eur J Histochem 58(4):2457. https://doi.org/10.4081/ejh.2014.2457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Porcher C, Baldo M, Henry M, Orsoni P, Jule Y, Ward SM (2002) Deficiency of interstitial cells of Cajal in the small intestine of patients with Crohn’s disease. Am J Gastroenterol 97(1):118–125. https://doi.org/10.1111/j.1572-0241.2002.05430.x

    Article  PubMed  Google Scholar 

  32. Yegutkin GG (2014) Enzymes involved in metabolism of extracellular nucleotides and nucleosides: functional implications and measurement of activities. Crit Rev Biochem Mol Biol 49(6):473–497. https://doi.org/10.3109/10409238.2014.953627

    Article  CAS  PubMed  Google Scholar 

  33. Antonioli L, Colucci R, Pellegrini C, Giustarini G, Sacco D, Tirotta E, Caputi V, Marsilio I, Giron MC, Németh ZH, Blandizzi C, Fornai M (2016) The AMPK enzyme-complex: from the regulation of cellular energy homeostasis to a possible new molecular target in the management of chronic inflammatory disorders. Expert Opin Ther Targets 20(2):179–191. https://doi.org/10.1517/14728222.2016.1086752

    Article  CAS  PubMed  Google Scholar 

  34. Pearson JD, Carleton JS, Gordon JL (1980) Metabolism of adenine nucleotides by ectoenzymes of vascular endothelial and smooth-muscle cells in culture. The Biochemical journal 190(2):421–429

    Article  CAS  Google Scholar 

  35. Gordon EL, Pearson JD, Dickinson ES, Moreau D, Slakey LL (1989) The hydrolysis of extracellular adenine nucleotides by arterial smooth muscle cells. Regulation of adenosine production at the cell surface. J Biol Chem 264(32):18986–18995

    CAS  PubMed  Google Scholar 

  36. Casali EA, da Silva TR, Gelain DP, Kaiser GR, Battastini AM, Sarkis JJ, Bernard EA (2001) Ectonucleotidase activities in Sertoli cells from immature rats. Braz J Med Biol Res 34(10):1247–1256

    Article  CAS  Google Scholar 

  37. Strohmeier GR, Lencer WI, Patapoff TW, Thompson LF, Carlson SL, Moe SJ, Carnes DK, Mrsny RJ, Madara JL (1997) Surface expression, polarization, and functional significance of CD73 in human intestinal epithelia. J Clin Invest 99(11):2588–2601. https://doi.org/10.1172/jci119447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Narravula S, Lennon PF, Mueller BU, Colgan SP (2000) Regulation of endothelial CD73 by adenosine: paracrine pathway for enhanced endothelial barrier function. J Immunol (Baltimore, Md: 1950) 165(9):5262–5268

    Article  CAS  Google Scholar 

  39. Allard B, Longhi MS, Robson SC, Stagg J (2017) The ectonucleotidases CD39 and CD73: novel checkpoint inhibitor targets. Immunol Rev 276(1):121–144. https://doi.org/10.1111/imr.12528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ferrari D, Gambari R, Idzko M, Muller T, Albanesi C, Pastore S, La Manna G, Robson SC, Cronstein B (2016) Purinergic signaling in scarring. FASEB J 30(1):3–12. https://doi.org/10.1096/fj.15-274563

    Article  CAS  PubMed  Google Scholar 

  41. Jackson EK, Cheng D, Verrier JD, Janesko-Feldman K, Kochanek PM (2014) Interactive roles of CD73 and tissue nonspecific alkaline phosphatase in the renal vascular metabolism of 5′-AMP. Am J Physiol Ren Physiol 307(6):F680–F685. https://doi.org/10.1152/ajprenal.00312.2014

    Article  CAS  Google Scholar 

  42. Zimmermann H, Zebisch M, Strater N (2012) Cellular function and molecular structure of ecto-nucleotidases. Purinergic Signal 8(3):437–502. https://doi.org/10.1007/s11302-012-9309-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Bilski J, Mazur-Bialy A, Wojcik D, Zahradnik-Bilska J, Brzozowski B, Magierowski M, Mach T, Magierowska K, Brzozowski T (2017) The role of intestinal alkaline phosphatase in inflammatory disorders of gastrointestinal tract. Mediat Inflamm 2017:9074601. https://doi.org/10.1155/2017/9074601

    Article  CAS  Google Scholar 

  44. Bhattarai S, Freundlieb M, Pippel J, Meyer A, Abdelrahman A, Fiene A, Lee SY, Zimmermann H, Yegutkin GG, Strater N, El-Tayeb A, Muller CE (2015) alpha, beta-Methylene-ADP (AOPCP) derivatives and analogues: development of potent and selective ecto-5′-nucleotidase (CD73) inhibitors. J Med Chem 58(15):6248–6263. https://doi.org/10.1021/acs.jmedchem.5b00802

    Article  CAS  PubMed  Google Scholar 

  45. Xu PA, Kellems RE (2000) Function of murine adenosine deaminase in the gastrointestinal tract. Biochem Biophys Res Commun 269(3):749–757. https://doi.org/10.1006/bbrc.2000.2357

    Article  CAS  PubMed  Google Scholar 

  46. Antonioli L, Fornai M, Awwad O, Giustarini G, Pellegrini C, Tuccori M, Caputi V, Qesari M, Castagliuolo I, Brun P, Giron MC, Scarpignato C, Blandizzi C, Colucci R (2014) Role of the A(2B) receptor-adenosine deaminase complex in colonic dysmotility associated with bowel inflammation in rats. Br J Pharmacol 171(5):1314–1329. https://doi.org/10.1111/bph.12539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Zamzow CR, Xiong W, Parkinson FE (2008) Adenosine produced by neurons is metabolized to hypoxanthine by astrocytes. J Neurosci Res 86(15):3447–3455. https://doi.org/10.1002/jnr.21789

    Article  CAS  PubMed  Google Scholar 

  48. Street SE, Kramer NJ, Walsh PL, Taylor-Blake B, Yadav MC, King IF, Vihko P, Wightman RM, Millan JL, Zylka MJ (2013) Tissue-nonspecific alkaline phosphatase acts redundantly with PAP and NT5E to generate adenosine in the dorsal spinal cord. J Neurosci 33(27):11314–11322. https://doi.org/10.1523/jneurosci.0133-13.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Araujo CL, Quintero IB, Kipar A, Herrala AM, Pulkka AE, Saarinen L, Hautaniemi S, Vihko P (2014) Prostatic acid phosphatase is the main acid phosphatase with 5′-ectonucleotidase activity in the male mouse saliva and regulates salivation. Am J Physiol Cell Physiol 306(11):C1017–C1027. https://doi.org/10.1152/ajpcell.00062.2014

    Article  CAS  PubMed  Google Scholar 

  50. Vieira C, Ferreirinha F, Silva I, Duarte-Araujo M, Correia-de-Sa P (2011) Localization and function of adenosine receptor subtypes at the longitudinal muscle--myenteric plexus of the rat ileum. Neurochem Int 59(7):1043–1055. https://doi.org/10.1016/j.neuint.2011.08.016

    Article  CAS  PubMed  Google Scholar 

  51. Caputi V, Marsilio I, Cerantola S, Roozfarakh M, Lante I, Galuppini F, Rugge M, Napoli E, Giulivi C, Orso G, Giron MC (2017) Toll-like receptor 4 modulates small intestine neuromuscular function through nitrergic and purinergic pathways. Front Pharmacol 8:350. https://doi.org/10.3389/fphar.2017.00350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Brun P, Gobbo S, Caputi V, Spagnol L, Schirato G, Pasqualin M, Levorato E, Palu G, Giron MC, Castagliuolo I (2015) Toll like receptor-2 regulates production of glial-derived neurotrophic factors in murine intestinal smooth muscle cells. Mol Cell Neurosci 68:24–35. https://doi.org/10.1016/j.mcn.2015.03.018

    Article  CAS  PubMed  Google Scholar 

  53. Vieira C, Ferreirinha F, Magalhaes-Cardoso MT, Silva I, Marques P, Correia-de-Sa P (2017) Post-inflammatory ileitis induces non-neuronal purinergic signaling adjustments of cholinergic neurotransmission in the myenteric plexus. Front Pharmacol 8:811. https://doi.org/10.3389/fphar.2017.00811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We thank Dr. Francesca Patrese and Dr. Ludovico Scenna for veterinary assistance; Mauro Berto, Massimo Rizza, and Andrea Pagetta for technical assistance in animal handling and experimental procedures.

Funding

This work was supported by grants from University of Padova (UNIPD-CPDR155591/15 Assegno di Ricerca 2016, UNIPD-DSF-DOR-2016 and 2017 funds, and UNIPD-DSF-PRID-2017) and from San Camillo Hospital, Treviso (Italy) to MCG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Author notes

  1. Anna Bin and Valentina Caputi contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo Meneghetti 2, 35131, Padova, Italy

    Anna Bin, Valentina Caputi, Monica Montopoli, Rocchina Colucci, Sara De Martin, Genny Orso, Patrizia Debetto & Maria Cecilia Giron

  2. APC Microbiome Ireland, University College Cork, Cork, Ireland

    Valentina Caputi

  3. Department of Medicine and Surgery, University of Insubria, Varese, Italy

    Michela Bistoletti & Cristina Giaroni

  4. Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126, Pisa, Italy

    Luca Antonioli

  5. Department of Molecular Medicine, University of Padova, Via Gabelli 63, 35121, Padova, Italy

    Ignazio Castagliuolo

  6. IRCCS “E. Medea” Bosisio Parini, Lecco, Italy

    Genny Orso

Authors
  1. Anna Bin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Valentina Caputi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michela Bistoletti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Monica Montopoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rocchina Colucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luca Antonioli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sara De Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ignazio Castagliuolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Genny Orso
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Cristina Giaroni
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Patrizia Debetto
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Maria Cecilia Giron
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceived and designed the experiments: MCG, AB, VC. Performed the experiments: AB, VC, IC, GO, MB. Analyzed the data: MCG, AB, VC, IC, GO, SDM, MM, LA, CG, RC, PD. Contributed reagents/materials/analysis tools: MCG, GO, IC, PD, CG. Wrote the manuscript: MCG, AB, VC. All the authors reviewed the manuscript.

Corresponding author

Correspondence to Maria Cecilia Giron.

Ethics declarations

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical approval

All experimental protocols were approved by the Animal Care and Use Committee of the University of Padova and by the Italian Ministry of Health and were in compliance with the national and EU guidelines for handling and use of experimental animals.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bin, A., Caputi, V., Bistoletti, M. et al. The ecto-enzymes CD73 and adenosine deaminase modulate 5′-AMP-derived adenosine in myofibroblasts of the rat small intestine. Purinergic Signalling 14, 409–421 (2018). https://doi.org/10.1007/s11302-018-9623-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11302-018-9623-6

Keywords

Search

Navigation