Nucleotides regulate NaCl transport in mIMCD-K2 cells via P2X and P2Y purinergic receptors

The involvement of purinergic signalling in kidney physiology and pathophysiology is rapidly gaining recognition and this is a comprehensive review of early and recent publications in the field. Purinergic signalling involvement is described in several important intrarenal regulatory mechanisms, including tuboglomerular feedback, the autoregulatory response of the glomerular and extraglomerular microcirculation and the control of renin release. Furthermore, purinergic signalling influences water and electrolyte transport in all segments of the renal tubule. Reports about purine-and pyrimidine-mediated actions in diseases of the kidney, including polycystic kidney disease, nephritis, diabetes, hypertension and nephrotoxicant injury are covered and possible purinergic therapeutic strategies discussed.

Section: Sodium Transportcontrasting

confidence: 70%

Purinergic signalling in the kidney in health and disease

Burnstock

Evans

Bailey

2013

“…Schwiebert et al also documented the appearance of P2X 7 to a significant degree at the mRNA level in primary cultures of human polycystic kidney disease (PKD) cells versus non-PKD human renal epithelial cell primary cultures as controls [101]. In a collaborative study with McCoy and Stanton, they showed expression of P2Y 1 and P2Y 2 as well as P2X 3 and P2X 4 in mIMCD-K2 cells [94]. In studies in mouse DCT cells by Quamme and coworkers and by Wingo and coworkers in mIMCD-3 cells, expression and function of both P2Y and P2X purinoceptors was concluded [92,93].…”

Section: Nucleotide and Nucleoside Receptor Expression Along The Nephronmentioning

confidence: 96%

“…P2X 6 is likely also expressed along most nephron segments, based on the work of Turner et al from the Unwin laboratory [86]. In collecting duct-cell models, the expression pattern shifted to P2X 3 and P2X 4 as the most abundantly expressed members [94,101]. Schwiebert et al also documented the appearance of P2X 7 to a significant degree at the mRNA level in primary cultures of human polycystic kidney disease (PKD) cells versus non-PKD human renal epithelial cell primary cultures as controls [101].…”

Section: Nucleotide and Nucleoside Receptor Expression Along The Nephronmentioning

confidence: 99%

Purinergic signaling in the lumen of a normal nephron and in remodeled PKD encapsulated cysts

Hovater

Olteanu

Welty

et al. 2008

Self Cite

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.

“…How such enhancements of P2X 4 -like receptor function might lead to a potentiation of renal ENaC activity is still to be resolved, but a hint comes from a series of interconnected findings. First, McCoy et al reported that ATP responses in mIMCD-K2 cells were biphasic and comprised an initial reduction in sodium transport, followed by a small secondary rise [37]. Second, similar biphasic responses to serosally applied ATP were observed in frog skin epithelium, where the initial reduction in sodium transport occurred at the same time as a transient elevation in intracellular calcium, but the secondary rise in sodium transport was associated with the apical insertion of new sodium channels [43].…”

Section: Enac Modulation By P2rs In the Kidneymentioning

confidence: 91%

“…All apically expressed P2Rs inhibit ENaC, although the ability of P2Y receptors to inhibit ENaC is less than that in a (from 49-56% to 16%). The potentiating effect of apical P2X 4/6 receptors (when luminal Na + is low) has not been investigated over a 30-min period, but a potentiating effect of basolaterally expressed P2X 4 -like receptors has been reported in the immortalised K2-cell line from mouse inner medullary CD (mIMCD) [37]. Here, ATP or UTP (100 µM) caused only a modest reduction (~15%).…”

Section: Enac Modulation By P2rs In the Kidneymentioning

confidence: 97%

ENaC, renal sodium excretion and extracellular ATP

Wildman

Kang

King

2009

Sodium balance determines the extracellular fluid volume and sets arterial blood pressure (BP). Chronically raised BP (hypertension) represents a major health risk in Western societies. The relationship between BP and renal sodium excretion (the pressure/natriuresis relationship) represents the key element in defining the BP homeostatic set point. The renin-angiotensin-aldosterone system (RAAS) makes major adjustments to the rates of renal sodium secretion, but this system works slowly over a period of hours to days. More rapid adjustments can be made by the sympathetic nervous system, although the kidney can function well without sympathetic nerves. Attention has now focussed on regulatory mechanisms within the kidney, including extracellular nucleotides and the P2 receptor system. Here, we discuss how extracellular ATP can control renal sodium excretion by altering the activity of epithelial sodium channels (ENaC) present in the apical membrane of principal cells. There remains considerable controversy over the molecular targets for released ATP, although the P2Y 2 receptor has received much attention. We review the available data and reflect on our own findings in which ATP-activated P2Y and P2X receptors make adjustments to ENaC activity and therefore sodium excretion.