Purinergic signaling in the lumen of a normal nephron and in remodeled PKD encapsulated cysts - PubMed (original) (raw)
Purinergic signaling in the lumen of a normal nephron and in remodeled PKD encapsulated cysts
Michael B Hovater et al. Purinergic Signal. 2008 Jun.
Abstract
The nephron is the functional unit of the kidney. Blood and plasma are continually filtered within the glomeruli that begin each nephron. Adenosine 5' triphosphate (ATP) and its metabolites are freely filtered by each glomerulus and enter the lumen of each nephron beginning at the proximal convoluted tubule (PCT). Flow rate, osmolality, and other mechanical or chemical stimuli for ATP secretion are present in each nephron segment. These ATP-release stimuli are also different in each nephron segment due to water or salt permeability or impermeability along different luminal membranes of the cells that line each nephron segment. Each of the above stimuli can trigger additional ATP release into the lumen of a nephron segment. Each nephron-lining epithelial cell is a potential source of secreted ATP. Together with filtered ATP and its metabolites derived from the glomerulus, secreted ATP and adenosine derived from cells along the nephron are likely the principal two of several nucleotide and nucleoside candidates for renal autocrine and paracrine ligands within the tubular fluid of the nephron. This minireview discusses the first principles of purinergic signaling as they relate to the nephron and the urinary bladder. The review discusses how the lumen of a renal tubule presents an ideal purinergic signaling microenvironment. The review also illustrates how remodeled and encapsulated cysts in autosomal dominant polycystic kidney disease (ADPKD) and remodeled pseudocysts in autosomal recessive PKD (ARPKD) of the renal collecting duct likely create an even more ideal microenvironment for purinergic signaling. Once trapped in these closed microenvironments, purinergic signaling becomes chronic and likely plays a significant epigenetic and detrimental role in the secondary progression of PKD, once the remodeling of the renal tissue has begun. In PKD cystic microenvironments, we argue that normal purinergic signaling within the lumen of the nephron provides detrimental acceleration of ADPKD once remodeling is complete.
Figures
Fig. 1
Nucleotide secretion along the nephron: current postulates. Although not pictured as such, the sources of secreted ATP along the nephron are the renal epithelial cells themselves that line each nephron segment
Fig. 2
Purinergic signaling in an encapsulated ADPKD cyst. The progression of remodeling in ARPKD versus ADPKD is shown in diagram format. Whereas some longer-lived extracellular ATP and adenosine (Ado) signaling may occur in dilated ARPKD segments, ADPKD cysts have lost communication with the rest of the nephron when encapsulated
Fig. 3
Postulated detrimental roles of purinergic signaling in an ARPKD pseudocyst or ADPKD cyst. Although ARPKD pseudocysts are not fully encapsulated, they may close off periodically due to limits in space between noncystic and cystic tissue parenchyma, leading to similar problems that occur in ADPKD encapsulated cysts. Adenosine stimulation of cyclic AMP and cystic fibrosis transmembrane-conductance-regulator (CFTR)-driven salt and water secretion and ATP stimulation of calcium-driven salt and water secretion are pictured, and both may proceed in parallel to the detriment of volume expansion in the cysts
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