Flow-Induced [Ca2+]i Increase Depends on Nucleotide Release and Subsequent Purinergic Signaling in the Intact Nephron

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: Renal Tubulesmentioning

confidence: 80%

Section: Release and Metabolism Of Nucleotidesmentioning

confidence: 96%

Section: Renal Tubulesmentioning

confidence: 99%

See 1 more Smart Citation

Purinergic signalling in the kidney in health and disease

Burnstock

Evans

Bailey

2013

“…poking at a cell) may cause damage and release of cellular content including ATP from the compromised cell. However, subtle non-destructive stimuli like gently rotating a dish with cultured cells [122], increasing the flow over an epithelial/endothelial sheet, or other gentle mechanical stimuli, are prominent triggers for nucleotide release [81,[123][124][125]. The field of astrocyte research has provided important clues in the recognition that a single cell mechanical stimulus can lead to waves of [Ca 2+ ] i increases spreading to neighbouring cells, which is caused by the spread of released nucleotides [36,90].…”

Section: Mechanically Released Nucleotidesmentioning

confidence: 99%

ATP release from non-excitable cells

Praetorius

Leipziger

2009

Self Cite

205

229

All cells release nucleotides and are in one way or another involved in local autocrine and paracrine regulation of organ function via stimulation of purinergic receptors. Significant technical advances have been made in recent years to quantify more precisely resting and stimulated adenosine triphosphate (ATP) concentrations in close proximity to the plasma membrane. These technical advances are reviewed here. However, the mechanisms by which cells release ATP continue to be enigmatic. The current state of knowledge on different suggested mechanisms is also reviewed. Current evidence suggests that two separate regulated modes of ATP release co-exist in nonexcitable cells: (1) a conductive pore which in several systems has been found to be the channel pannexin 1 and (2) vesicular release. Modes of stimulation of ATP release are reviewed and indicate that both subtle mechanical stimulation and agonist-triggered release play pivotal roles. The mechano-sensor for ATP release is not yet defined.

“…Nucleotide release into the luminal flow of the renal tubule can also be induced by hormones, such as AVP [73]. The released nucleotides are thought to follow the direction of flow and also affect P2 receptors in more distal parts of the nephron where the signal is finally disrupted by degrading enzymes, f ex CD73 [15,74,75].…”

Section: Flow-sensing Mechanisms Of Renal Tubular Epithelial Cellsmentioning

confidence: 99%

The touching story of purinergic signaling in epithelial and endothelial cells

Öhman

Erlinge

2012

Endothelial and epithelial cells have something in commonthey are both the barrier and bridge between different environments. Forming a one-cell layer lining of blood vessels, airways, and urinary tract, they are in constant contact with a wide variety of cells, putting high demands on the communication skills of these cells. The purinergic signaling system offers a dynamic and versatile way for local and rapid intercellular communication and involves three processes: nucleotide release, enzymatic degradation, and activation of purinergic receptors. With an impressive number of molecular members of the system (15 P2 receptor subtypes and in total 16 nucleotide-degrading enzymes), cells have managed to put purines and pyrimidines as well as their derivatives to use in an array of different areas, including regulation of flow, secretion, and vascular tone. Indeed, the purinergic signaling system is an ancient way of intercellular communication that most likely could be found in the first most primitive life form [1]. The scope of this review is to give an overview of exciting features of purinergic signaling and examples of gaps to fill in understanding its role in the cells lining the body-the endothelium and the epithelium. Purinergic signaling-an overviewExtracellular nucleotides exert their paracrine signaling by binding to P2 receptors present at the cell surface. The P2 receptor family is divided into two groups: P2X receptors, which are ligand-activated ion channels, and P2Y receptors, which are G protein-coupled receptors (reviewed in [2]). Each receptor is characterized by its affinity pattern for different nucleotides and different cell types display varying receptor profiles. While P2X receptors respond only to ATP, P2Y receptors can be activated by other nucleotides such as ADP, UTP, and UDP. Extracellular nucleotide concentrations are precisely regulated by ecto-enzymes, which cleave nucleotide tri-/diphosphates. The result of signaling by the extracellular nucleotides ATP/ADP, UTP/UDP and the nucleoside adenosine is both acute, for example the rapid platelet aggregation induced by ADP, and chronic, via changes in gene expression induced by P2 receptor stimulation. Ligand availability for P2 receptors is regulated by a group of enzymes termed ectonucleotidases. NTPDase1 (apyrase; CD39) cleaves ATP to AMP, NTPDase2 (CD39L1) cleaves ATP to ADP, and 5′-ectonucleotidase (CD73) generates adenosine from AMP. Adenosine is the end product of purinergic signaling, acting on adenosine receptors (A1, A2a, A2b, and A3; also termed P1 receptors) or recycling by the cell after reuptake through the equilibrating nucleoside transporters ENT1 and 2. UTP is believed to be released simultaneously with ATP via the same mechanism but at a lower concentration (UTP/ATP, 1:10-100). UTP is degraded in the same way as ATP, but the biological function of uridine is poorly understood and no uridine receptor has been identified. Figure 1 shows an outline of nucleotide metabolism. Purinergic toneAll investigators that have tried t...