1. Autocrine extracellular purinergic signaling in epithelial cells derived from polycystic kidneys
- Author
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Schwiebert, Erik M., Wallace, Darren P., Braunstein, Gavin M., King, Sandi R., Peti-Peterdi, Janos, Hanaoka, Kazushige, Guggino, William B., Guay-Woodford, Lisa M., Bell, P. Darwin, Sullivan, Lawrence P., Grantham, Jared J., and Taylor, Amanda L.
- Subjects
Autocrine mechanisms -- Research ,Epithelial cells -- Research ,Polycystic kidney disease -- Physiological aspects ,Adenosine triphosphate -- Research ,Biological sciences - 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 [Ca.sup.2+] concentration and secretory [Cl.sup.-] transport show P2Y and P2X purinergic receptor-mediated stimulation of [Cl.sup.-] secretion via cytosolic [Ca.sup.2+]-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. polycysfic kidney disease; adenosine 5'-triphosphate; autocrine; epithelia; purinergic receptors
- Published
- 2002