PGE2 stimulates CI? secretion in murine M-1 cortical collecting duct cells in an autocrine manner

Sandrasagra, Sabrina; Cuffe, John E.; Regardsoe, E. L.; Korbmacher, Christoph

doi:10.1007/s00424-004-1260-y

Cited by 11 publications

(20 citation statements)

References 63 publications

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“…16,18 EP2 has also been localized to mouse CCD cells, 14 the rabbit CCD, 33 and the human connecting tubule, 20 but kidney EP2 localization in mouse, rabbit, and human CDs is not consistently found. 13,14,21,22,33 EP2 is also expressed in renomedullary interstitial cells. 33 EP2 couples to Gs and signals through the second messenger cAMP.…”

Section: Postobstructive Polyuriamentioning

confidence: 99%

“…Butaprost increased ser-256 phosphorylation of AQP2 in cortical tubule suspensions and increased apical membrane accumulation of AQP2 in rat kidney slices, 18 indicating that EP2 is expressed in the CD, which has previously been an issue of some debate. 13,14,16,[18][19][20][21][22][23] This notion was further strengthened by the finding that butaprost was able to decrease polyuria in a rat model of x-linked NDI. Together, EP2 and EP4 are potential candidates for mediating urinary concentration in conditions with absent V2R signaling, but whether they can act alongside VP to increase urine concentration remains unknown.…”

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confidence: 96%

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Is There a Role for PGE2 in Urinary Concentration?

Olesen

Fenton

2013

Journal of the American Society of Nephrology

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Prostanoids are prominent, yet complex, components in the maintenance of body water homeostasis. Recent functional and molecular studies have revealed that the local lipid mediator PGE2 is involved both in water excretion and absorption. The biologic actions of PGE2 are exerted through four different G-protein-coupled receptors; designated EP1-4, which couple to separate intracellular signaling pathways. Here, we discuss new developments in our understanding of the actions of PGE2 that have been uncovered utilizing receptor specific agonists and antagonists, EP receptor and PG synthase knockout mice, polyuric animal models, and the new understanding of the molecular regulation of collecting duct water permeability. The role of PGE2 in urinary concentration comprises a variety of mechanisms, which are not fully understood and likely depend on which receptor is activated under a particular physiologic condition. EP3 and microsomal PG synthase type 1 play a role in decreasing collecting duct water permeability and increasing water excretion, whereas EP2 and EP4 can bypass vasopressin signaling and increase water reabsorption through two different intracellular signaling pathways. PGE2 has an intricate role in urinary concentration, and we now suggest how targeting specific prostanoid receptor signaling pathways could be exploited for the treatment of disorders in water balance. The neurohypophyseal hormone, vasopressin (VP), is a major regulator of renal water excretion, predominantly through the seven trans-membrane receptor (7TMR) V2R. It binds to Gas, inducing the cAMP second messenger system, resulting in increased NaCl absorption by the thick ascending limb and increased urea transport in the inner medullary collecting ducts (IMCDs). [1][2][3] In addition, VP induces accumulation of the water channel aquaporin-2 (AQP2) in the rate-limiting apical plasma membrane of collecting duct (CD) principal cells, 4 a process that involves a diverse range of post-translational modifications including phosphorylation of AQP2. 5 Thus, VP increases the osmotic gradient for water transport and the water permeability (Pf) of the CD simultaneously.In addition to systemic hormones, local regulatory factors play a role in the CD, of which PGE2 (Figure 1) is the focus of this review. 6-9 PGE2 has a diverse range of biologic actions elicited by four different 7TMRs. The renal localization of EP receptors and intracellular signaling pathways are diverse (Table 1). Here, we propose that urinary concentration does not rely exclusively on fluctuations in plasma VP concentrations, but that the locally derived lipid mediator, PGE2, plays an important role in regulating water excretion. PGE2 IN THE MODULATION OF URINARY CONCENTRATING MECHANISMSThe ability of PGE2 to modulate the effects of VP in the CD has been described in a range of experimental studies and discussed in previous reviews. [36][37][38][39] The present focus is on understanding the mechanisms for this effect, and on recent in vivo studies elucidating the role of P...

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Section: Postobstructive Polyuriamentioning

confidence: 99%

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confidence: 96%

Is There a Role for PGE2 in Urinary Concentration?

Olesen

Fenton

2013

Journal of the American Society of Nephrology

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“…This could be due to the high basal activity of adenylate cyclase that results in an increase in cell surface expression of AQP2. The higher adenylate cyclase activity can be due to stimulation of the EP4 receptor by prostaglandin E2 (PGE2) endogenously produced by M-1 cells (Nasrallah et al, 2001;Sandrasagra et al, 2004). To maintain low levels of cAMP at resting condition, cells were preincubated with the cyclooxigenase inhibitor indomethacin before each experiment.…”

Section: Aqp2 Trafficking In Mcd4 Cellsmentioning

confidence: 99%

AQP2 exocytosis in the renal collecting duct – involvement of SNARE isoforms and the regulatory role of Munc18b

Procino

Barbieri

Tamma

et al. 2008

Journal of Cell Science

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Vasopressin regulates the fusion of the water channel aquaporin 2 (AQP2) to the apical membrane of the renal collecting-duct principal cells and several lines of evidence indicate that SNARE proteins mediate this process. In this work MCD4 renal cells were used to investigate the functional role of a set of Q- and R-SNAREs, together with that of Munc18b as a negative regulator of the formation of the SNARE complex. Both VAMP2 and VAMP3 were associated with immunoisolated AQP2 vesicles, whereas syntaxin 3 (Stx3), SNAP23 and Munc18 were associated with the apical plasma membrane. Co-immunoprecipitation experiments indicated that Stx3 forms complexes with VAMP2, VAMP3, SNAP23 and Munc18b. Protein knockdown coupled to apical surface biotinylation demonstrated that reduced levels of the R-SNAREs VAMP2 and VAMP3, and the Q-SNAREs Stx3 and SNAP23 strongly inhibited AQP2 fusion at the apical membrane. In addition, knockdown of Munc18b promoted a sevenfold increase of AQP2 fused at the plasma membrane without forskolin stimulation. Taken together these findings propose VAMP2, VAMP3, Stx3 and SNAP23 as the complementary set of SNAREs responsible for AQP2-vesicle fusion into the apical membrane, and Munc18b as a negative regulator of SNARE-complex formation in renal collecting-duct principal cells.

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“…As a consequence, increased growth and transport are observed in AD-PKD tubular cells (33). PGE 2 similarly increases growth and Na ϩ transport in MDCK cells, as well as chloride secretion in MDCK cells, the murine M-1 cortical collecting duct cell line, and polycystin 1-deficient murine inner medullary collecting duct cells (33,46,50,51,59). We do not yet know whether these PGE 2 -mediated signaling events are altered in ADPKD.…”

Section: Discussionmentioning

confidence: 97%

Antagonism of the prostaglandin E₂ EP1 receptor in MDCK cells increases growth through activation of Akt and the epidermal growth factor receptor

Taub

Parker

Mathivanan

et al. 2014

American Journal of Physiology-Renal Physiology

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Taub M, Parker R, Mathivanan P, Ariff MA, Rudra T. Antagonism of the prostaglandin E 2 EP1 receptor in MDCK cells increases growth through activation of Akt and the epidermal growth factor receptor. Am J Physiol Renal Physiol 307: F539 -F550, 2014. First published July 9, 2014; doi:10.1152/ajprenal.00510.2013.-The actions of prostaglandin E 2 (PGE2) in the kidney are mediated by G protein-coupled E-prostanoid (EP) receptors, which affect renal growth and function. This report examines the role of EP receptors in mediating the effects of PGE 2 on Madin-Darby canine kidney (MDCK) cell growth. The results indicate that activation of Gscoupled EP2 and EP4 by PGE 2 results in increased growth, while EP1 activation is growth inhibitory. Indeed, two EP1 antagonists (ONO-8711 and SC51089) stimulate, rather than inhibit, MDCK cell growth, an effect that is lost following an EP1 knockdown. Similar observations were made with M1 collecting duct and rabbit kidney proximal tubule cells. ONO-8711 even stimulates growth in the absence of exogenous PGE 2, an effect that is prevented by ibuprofen (indicating a dependence upon endogenous PGE 2). The involvement of Akt was indicated by the observation that 1) ONO-8711 and SC51089 increase Akt phosphorylation, and 2) MK2206, an Akt inhibitor, prevents the increased growth caused by ONO-8711. The involvement of the EGF receptor (EGFR) was indicated by 1) the increased phosphorylation of the EGFR caused by SC51089 and 2) the loss of the growthstimulatory effect of ONO-8711 and SC51089 caused by the EGFR kinase inhibitor AG1478. The growth-stimulatory effect of ONO-8711 was lost following an EGFR knockdown, and transduction of MDCK cells with a dominant negative EGFR. These results support the hypothesis that 1) signaling via the EP1 receptor involves Akt as well as the EGFR, and 2), EP1 receptor pharmacology may be employed to prevent the aberrant growth associated with a number of renal diseases. prostaglandin E2; kidney epithelial cell growth; EP receptors PROSTAGLANDIN E2 (PGE2), the predominant product of arachidonic acid in the kidney, controls renal function by a number of different means (5). PGE 2 regulates salt and water reabsorption by tubular epithelial cells, glomerular filtration (41), renal blood flow (34), and the renin-angiotensin system (11). In addition, PGE 2 has been implicated as playing a role in the progression of a number of renal diseases, including diabetic nephropathy (36), glomerulonephritis (44), and autosomal dominant polycystic kidney disease (ADPKD) (33).The effects of PGE 2 are mediated by its interaction with four different subtypes of G protein-coupled EP receptors (8), including Gs-coupled EP2 and EP4, which activate adenylate cyclase (AC), Gi-coupled EP3, coupled to Gi, which reduces AC activity as well as Gq-coupled EP1, which activates PLC, resulting in an increase in intracellular Ca 2ϩ , and the activation of PKC. All four subtypes of EP receptors are present in the kidney (9). Especially high levels of EP1, EP3, and EP4 are present in the col...

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PGE2 stimulates CI? secretion in murine M-1 cortical collecting duct cells in an autocrine manner

Cited by 11 publications

References 63 publications

Is There a Role for PGE2 in Urinary Concentration?

Is There a Role for PGE2 in Urinary Concentration?

AQP2 exocytosis in the renal collecting duct – involvement of SNARE isoforms and the regulatory role of Munc18b

Antagonism of the prostaglandin E₂ EP1 receptor in MDCK cells increases growth through activation of Akt and the epidermal growth factor receptor

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PGE2 stimulates CI? secretion in murine M-1 cortical collecting duct cells in an autocrine manner

Cited by 11 publications

References 63 publications

Is There a Role for PGE2 in Urinary Concentration?

Is There a Role for PGE2 in Urinary Concentration?

AQP2 exocytosis in the renal collecting duct – involvement of SNARE isoforms and the regulatory role of Munc18b

Antagonism of the prostaglandin E2 EP1 receptor in MDCK cells increases growth through activation of Akt and the epidermal growth factor receptor

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Antagonism of the prostaglandin E₂ EP1 receptor in MDCK cells increases growth through activation of Akt and the epidermal growth factor receptor