The Journal of Physiological Sciences

, Volume 69, Issue 1, pp 85–95 | Cite as

Mechanism of luminal ATP activated chloride secretion in a polarized epithelium

  • N. Keating
  • K. Dev
  • A. C. Hynes
  • L. R. QuinlanEmail author
Original Paper


There are both secretory and absorptive pathways working in tandem to support ionic movement driving fluid secretion across epithelia. The mechanisms exerting control of fluid secretion in the oviduct is yet to be fully determined. This study explored the role of apical or luminal extracellular ATP (ATPe)-stimulated ion transport in an oviduct epithelium model, using the Ussing chamber short-circuit current (Isc) technique. Basal Isc in oviduct epithelium in response to apical ATPe comprises both chloride secretion and sodium absorption and has distinct temporal phases. A rapid transient peak followed by a sustained small increase above baseline. Both phases of the apical ATPe Isc response are sensitive to anion (HCO3, Cl) and cation (Na+) replacement. Additionally, the role of apical chloride channels, basolateral potassium channels and intracellular calcium in supporting the peak Isc current was confirmed. The role of ATP breakdown to adenosine resulting in the activation of P2 receptors was supported by examining the effects of non-hydrolyzable forms of ATP. A P2YR2 potency profile of ATP = UTP > ADP was generated for the apical membrane, suggesting the involvement of the P2YR2 subtype of purinoceptor. A P2X potency profile of ATP = 2MeSATP > alpha,beta-meATP > BzATP was also generated for the apical membrane. In conclusion, these results provide strong evidence that purinergic activation of apical P2YR2 promotes chloride secretion and is thus an important factor in fluid formation by the oviduct.


Oviduct epithelium Chloride secretion ATP Calcium signaling Potassium channels Chloride channels Purinoceptors 



This work was partly funded by the Millennium Research Fund, National University of Ireland, Galway.

Compliance with ethical standards

Conflict of interest

All Authors declare no conflicts of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.


  1. 1.
    Keating N, Quinlan LR (2008) Effect of basolateral adenosine triphosphate on chloride secretion by bovine oviductal epithelium. Biol Reprod 78:1119–1126. CrossRefGoogle Scholar
  2. 2.
    Borland RM, Biggers JD, Lechene CP, Taymor ML (1980) Elemental composition of fluid in the human Fallopian-tube. J Reprod Fertil 58:479–482CrossRefGoogle Scholar
  3. 3.
    Tay JI, Rutherford AJ, Killick SR et al (1997) Human tubal fluid: production, nutrient composition and response to adrenergic agents. Hum Reprod 12:2451–2456CrossRefGoogle Scholar
  4. 4.
    Keating N, Quinlan LR (2012) Small conductance potassium channels drive ATP-activated chloride secretion in the oviduct. Am J Physiol Cell Physiol 302:C100–C109. CrossRefGoogle Scholar
  5. 5.
    Leese HJ, Tay JI, Reischl J, Downing SJ (2001) Formation of Fallopian tubal fluid: role of a neglected epithelium. Reproduction 121:339–346CrossRefGoogle Scholar
  6. 6.
    Dickens CJ, Comer MT, Southgate J, Leese HJ (1996) Human Fallopian tubal epithelial cells in vitro: establishment of polarity and potential role of intracellular calcium and extracellular ATP in fluid secretion. Hum Reprod 11:212–217CrossRefGoogle Scholar
  7. 7.
    Dickens CJ, Leese HJ (1994) The regulation of rabbit oviduct fluid formation. J Reprod Fertil 100:577–581CrossRefGoogle Scholar
  8. 8.
    Ajonuma LC, Ng EHY, Chow PH et al (2005) Increased cystic fibrosis transmembrane conductance regulator (CFTR) expression in the human hydrosalpinx. Hum Reprod 20:1228–1234. CrossRefGoogle Scholar
  9. 9.
    Glasser SR, Mulholland J (1993) Receptivity is a polarity dependent special function of hormonally regulated uterine epithelial-cells. Microsc Res Tech 25:106–120. CrossRefGoogle Scholar
  10. 10.
    Barrett KE (1993) Positive and negative regulation of chloride secretion in T84 cells. Am J Physiol Regul Integr Comp Physiol 265:859–868CrossRefGoogle Scholar
  11. 11.
    Aliagas E, Torrejón-Escribano B, Lavoie EG et al (2010) Changes in expression and activity levels of ecto-5′-nucleotidase/CD73 along the mouse female estrous cycle. Acta Physiol 199:191–197. CrossRefGoogle Scholar
  12. 12.
    Praetorius HA, Leipziger J (2010) Intrarenal purinergic signaling in the control of renal tubular transport. Annu Rev Physiol 72:377–393. CrossRefGoogle Scholar
  13. 13.
    Burnstock G (2006) Pathophysiology and therapeutic potential of purinergic signaling. Pharmacol Rev 58:58–86. CrossRefGoogle Scholar
  14. 14.
    Bucheimer RE, Linden J (2004) Purinergic regulation of epithelial transport. J Physiol 555:311–321. CrossRefGoogle Scholar
  15. 15.
    Yu H, Bianchi B, Metzger R, et al (1999) Lack of specificity of [35S]‐ATPγS and [35S]‐ADPβS as radioligands for ionotropic and metabotropic P2 receptor binding. Drug Development Research 48:84–93.<84:aid-ddr6>;2-wGoogle Scholar
  16. 16.
    Cuffe JE, Bielfeld-Ackermann A, Thomas J et al (2000) ATP stimulates Clsecretion and reduces amiloride-sensitive Na+absorption in M-1 mouse cortical collecting duct cells. J Physiol (Lond) 524:77–90. CrossRefGoogle Scholar
  17. 17.
    Palmer-Densmore M, Deachapunya C, Kannan M, O’Grady SM (2002) UTP-dependent inhibition of Na+ absorption requires activation of PKC in endometrial epithelial cells. J Gen Physiol 120:897–906. CrossRefGoogle Scholar
  18. 18.
    Chan HC, Shi QX, Zhou CX et al (2006) Critical role of CFTR in uterine bicarbonate secretion and the fertilizing capacity of sperm. Mol Cell Endocrinol 250:106–113. CrossRefGoogle Scholar
  19. 19.
    Wang XF, Zhou CX, Shi QX et al (2003) Involvement of CFTR in uterine bicarbonate secretion and the fertilizing capacity of sperm. Nat Cell Biol 5:902–906. CrossRefGoogle Scholar
  20. 20.
    Chan LN, Wang XF, Tsang LL, Chan HC (2000) Pyrimidinoceptors-mediated activation of Ca(2 +) -dependent Cl (−) conductance in mouse endometrial epithelial cells. Biochimica et Biophysica Acta (BBA)—molecular. Cell Res 1497:261–270. Google Scholar
  21. 21.
    Zsembery A, Sitter G, Jessner W et al (2000) Correction of defective CFTR function in bile ductular cells from a patient with cystic fibrosis. J Hepatol 32:208–209CrossRefGoogle Scholar
  22. 22.
    Clarke LL, Harline MC, Gawenis LR et al (2000) Extracellular UTP stimulates electrogenic bicarbonate secretion across CFTR knockout gallbladder epithelium. Am J Physiol 279:G132–G138. Google Scholar
  23. 23.
    Al-Nakkash L, Cotton CU (1997) Bovine pancreatic duct cells express cAMP- and Ca(2 +)-activated apical membrane Cl− conductances. American Journal of Physiology-Gastrointestinal and Liver. Physiology 273:G204–G216. Google Scholar
  24. 24.
    Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50:413–492Google Scholar
  25. 25.
    Bianchi BR, Lynch KJ, Touma E et al (1999) Pharmacological characterization of recombinant human and rat P2X receptor subtypes. Eur J Pharmacol 376:127–138. CrossRefGoogle Scholar
  26. 26.
    Bo X, Jiang L-H, Wilson HL et al (2003) Pharmacological and biophysical properties of the human P2X5 receptor. Mol Pharmacol 63:1407–1416. CrossRefGoogle Scholar
  27. 27.
    Barrett KE, Smitham J, Traynor-Kaplan A, Uribe JM (1998) Inhibition of Ca2+ -dependent Clsecretion in T84 cells: membrane target(s) of inhibition is agonist specific. Am J Physiol 274:C958–C965. CrossRefGoogle Scholar
  28. 28.
    Carew MA, Yang XN, Schultz C, Shears SB (2000) Myo-inositol 3,4,5,6-tetrakisphosphate inhibits an apical calcium-activated chloride conductance in polarized monolayers of a cystic fibrosis cell line. J Biol Chem 275:26906–26913. Google Scholar
  29. 29.
    Ho M, Kaetzel MA, Armstrong DL, Shears SB (2001) Regulation of a human chloride channel—a paradigm for integrating input from calcium, type II calmodulin-dependent protein kinase, and inositol 3,4,5,6-tetrakisphosphate. J Biol Chem 276:18673–18680. CrossRefGoogle Scholar
  30. 30.
    Smitham JE, Barrett KE (1998) Differential effects of uridine triphosphate on intestinal chloride secretion depending on side of addition: implications for cystic fibrosis therapy. YGAST 114:A417–A418. Google Scholar

Copyright information

© The Physiological Society of Japan and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  • N. Keating
    • 1
  • K. Dev
    • 1
  • A. C. Hynes
    • 1
  • L. R. Quinlan
    • 1
    • 2
    Email author
  1. 1.Physiology, School of MedicineNational University of Ireland, GalwayGalwayIreland
  2. 2.CÚRAM, Centre for Research in Medical DevicesNUI GalwayGalwayIreland

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