Autocrine extracellular purinergic signaling in epithelial cells derived from polycystic kidneys

Erik M. Schwiebert, Darren P. Wallace, Gavin M. Braunstein, Sandi R. King, Janos Peti-Peterdi, Kazushige Hanaoka, William B. Guggino, Lisa M. Guay-Woodford, P. Darwin Bell, Lawrence P. Sullivan, Jared J. Grantham, Amanda L. Taylor

Research output: Contribution to journalArticle

Abstract

ATP and its metabolites are potent autocrine agonists that act extracellularly within tissues to affect epithelial function. In polycystic kidneys, renal tubules become dilated and/or encapsulated as cysts, creating abnormal microenvironments for autocrine signaling. Previously, our laboratory has shown that high-nanomolar to micromolar quantities of ATP are released from cell monolayers in vitro and detectable in cyst fluids from microdissected human autosomal dominant polycystic kidney (ADPKD) cysts. Here, we show enhanced ATP release from autosomal recessive polycystic kidney (ARPKD) and ADPKD epithelial cell models. RT-PCR and immunoblotting for P2Y G protein-coupled receptors and P2X purinergic receptor channels show expression of mRNA and/or protein for multiple subtypes from both families. Assays of cytosolic Ca2+ concentration and secretory Cl- transport show P2Y and P2X purinergic receptor-mediated stimulation of Cl- secretion via cytosolic Ca2+-dependent signaling. Therefore, we hypothesize that autocrine purinergic signaling may augment detrimentally cyst volume expansion in ADPKD or tubule dilation in ARPKD, accelerating disease progression.

Original languageEnglish (US)
Pages (from-to)F763-F775
JournalAmerican Journal of Physiology - Renal Physiology
Volume282
Issue number4 51-4
StatePublished - Jun 29 2002

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Keywords

  • Adenosine 5′-triphosphate
  • Autocrine
  • Epithelia
  • Polycystic kidney disease
  • Purinergic receptors

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Schwiebert, E. M., Wallace, D. P., Braunstein, G. M., King, S. R., Peti-Peterdi, J., Hanaoka, K., Guggino, W. B., Guay-Woodford, L. M., Darwin Bell, P., Sullivan, L. P., Grantham, J. J., & Taylor, A. L. (2002). Autocrine extracellular purinergic signaling in epithelial cells derived from polycystic kidneys. American Journal of Physiology - Renal Physiology, 282(4 51-4), F763-F775.