Prostaglandin E2 inhibits sodium transport in rabbit cortical collecting duct by increasing intracellular calcium.

Hébert, Richard; Jacobson, Howard; Breyer, Matthew D.

doi:10.1172/jci115227

Cited by 123 publications

(87 citation statements)

References 37 publications

(23 reference statements)

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“…Indeed, enhanced Na,K-ATPase activity has been reported in isolated microdisected rat distal tubules following PGE 2 treatment [55]. In our own studies we observed that PGE 1 and PGE 2 increase the Na,K-ATPase activity of MDCK cells which model cells in the distal tubule.…”

Section: Discussionsupporting

confidence: 49%

Involvement of EP1 and EP2 receptors in the regulation of the Na,K-ATPase by prostaglandins in MDCK cells

Matlhagela

Taub

2006

Prostaglandins & Other Lipid Mediators

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Prostaglandins are key regulators of ion transport in the kidney. In MDCK cells, which model distal tubule cells, the transcription of the Na,K-ATPase β1 subunit is regulated by PGE 1 and PGE 2 . To identify the EP receptors that mediate transcriptional regulation, transient transfection studies are conducted using the human β1 promoter/luciferase construct, pHβ1-1141 Luc. The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE 2 , and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific). Consistent with the involvement of Gs coupled EP2 receptors, is that the PGE 1 stimulation is inhibited by the PKAI expression vector (encoding the protein kinase A (PKA) inhibitory protein), as well as by the myristolated PKA inhibitory peptide PKI. In addition to this evidence (for the involvement of EP2 receptors), evidence for the involvement of EP1 receptors in the PGE 1 mediated stimulation of Na,KATPase β subunit gene transcription includes the stimulatory effect of 17-phenyl trinor PGE 2 , as well as the inhibitory effects of SC-51089. Also consistent with the involvement of Gq coupled EP1 receptors, the PGE 1 stimulation is inhibited by the PKCI vector (encoding the PKC inhibitory domain), the PKC inhibitor Go 6976, thapsigargin, as well as the calmodulin antagonists W7 and W13.

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Section: Discussionsupporting

confidence: 49%

Involvement of EP1 and EP2 receptors in the regulation of the Na,K-ATPase by prostaglandins in MDCK cells

Matlhagela

Taub

2006

Prostaglandins & Other Lipid Mediators

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“…While EP 1 , FP and TP receptors are also abundantly expressed in the kidney (Sugimoto et al, 2000) and they are each reported to mediate efficient contraction of renal vascular SM and mesangial cells through Ca 2 þ -dependent mechanisms (Mene et al, 1989), their role in renal function as garnered from mouse knockout studies remains to be clearly established. While the precise intrarenal distribution of the FP has not yet been reported, in situ hybridization has localized the EP 1 largely to the cortical collecting duct (Hebert et al, 1991;Hebert, 1994). Similarly, in situ hybridization studies in the rat confirmed the abundant expression of the TP within the glomerulus, arterioles and epithelium lining the urinary pelvis and an absence of/reduced expression in the proximal tubule, cortical thick limb or the collecting duct (Abe et al, 1995).…”

Section: Discussionmentioning

confidence: 90%

EP₁‐ and FP‐mediated cross‐desensitization of the alpha (α) and beta (β) isoforms of the human thromboxane A₂ receptor

Kelley-Hickie

Kinsella

2004

British J Pharmacology

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1 Heterologous desensitization or intermolecular cross-talk plays a critical role in regulating intracellular signalling by diverse members of the G-protein-coupled receptor superfamily. We have previously established that the a and b isoforms of the human thromboxane A 2 receptor (TP) undergo differential desensitization of signalling in response to 17 phenyl trinor prostaglandin (PG)E 2 , an agonist of the EP 1 subtype of the PGE 2 receptor (EP) family. 2 Herein, we investigated the molecular basis of TPa and TPb desensitization in human embryonic kidney (HEK) 293 cells and in renal mesangial cells in response to 17 phenyl trinor PGE 2 and in response to the PGF 2a receptor (FP) agonist PGF 2a , and sought to identify the target site(s) of those desensitizations.3 Our results demonstrated that TPa and TPb receptors are subject to desensitization in response to both EP 1 and FP receptor activation and that these effects are mediated by direct protein kinase (PK)C phosphorylation of the individual TP isoforms within their unique carboxyl-terminal (C)-tail domains. 4 Moreover, deletion/site-directed mutagenesis and metabolic labelling studies identified Thr 337 , within TPa, and Thr 399 , within TPb, as the specific target residues for PKC phosphorylation and EP 1 -and FP-mediated desensitization of TPa and TPb signalling, respectively. 5 Hence, in conclusion, while the TPa and TPb diverge within their C-tail domains, they have evolved to share a similar mechanism of PKC-induced phosphorylation and desensitization in response to EP 1 and FP receptor activation, though it occurs at sites unique to the individual TP isoforms.

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“…Along the nephron, the EP 1 receptor is abundantly expressed in the principal cells of the collecting duct, where it is thought to offset the buffering influence of EP 3 receptors upon the anti-diuretic actions of AVP (31). In vitro studies showed that PGE 2 can inhibit sodium transport in the isolated, perfused rabbit collecting duct by a mechanism coupled to the release of Ca 2ϩ from intracellular stores, consistent with EP 1 -mediated signal transduction (14). In contrast, work by Coffman and colleagues (29) supports an anti-natriuretic role for the EP 1 receptor.…”

Section: F872mentioning

confidence: 81%

Urine concentrating defect in prostaglandin EP₁-deficient mice

Kennedy¹,

Xiong²,

Rahal³

et al. 2007

American Journal of Physiology-Renal Physiology

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We investigated the role of the prostaglandin E2 (PGE2) EP1 receptor in modulating urine concentration as it is expressed along the renal collecting duct where argininevasopressin (AVP) exerts its anti-diuretic activity, and in the paraventricular and supraoptic nuclei of the hypothalamus where AVP is synthesized. The urine osmolality of EP 1-null mice (EP1 Ϫ/Ϫ ) failed to match levels achieved by wild-type (WT) counterparts upon water deprivation (WD) for 24 h. This difference was reflected by higher plasma osmolality in WD EP 1 Ϫ/Ϫ mice. Along the collecting duct, the induction and subapical to plasma membrane translocation of the aquaporin-2 water channel in WD EP Ϫ/Ϫ mice. When mice were water loaded to suppress endogenous AVP production, urine osmolalities increased equally for WT and EP 1 Ϫ/Ϫ mice. These data suggest that PGE 2 modulates urine concentration by acting at EP 1 receptors, not in the collecting duct, but within the hypothalamus to promote AVP synthesis in response to acute WD. vasopressin; urine concentration; prostaglandin E 2; EP1 receptor URINE CONCENTRATION IS A HIGHLY regulated process requiring the coordinated actions of a number of hormones at several tissue locales (2). The body responds to acute volume depletion, infection, or hyperosmolality by stimulating the production of antidiuretic hormone, arginine-vasopressin (AVP), within the hypothalamic paraventricular (PVN) and supraoptic (SON) neurons. AVP is then processed, stored, and secreted into the venous flow by the posterior pituitary to interact with renal V 2 receptors located in the principal cells of the collecting duct to promote aquaporin-2 (AQP2)-dependent water reabsorption (25). Many of these steps are subject to modulation by endocrine factors such as ANG II, catecholamines, as well as certain metabolites of the cyclooxygenase (COX) pathway, the prostaglandins (PGs) (2). Accordingly, renal prostaglandin E 2 (PGE 2 ) antagonizes the actions of AVP since NSAIDs transiently enhance urine concentration (1). Direct evidence for the underlying mechanism was provided by who demonstrated that PGE 2 attenuates vasopressin-stimulated osmotic water reabsorption in isolated microperfused rabbit collecting ducts. Subsequent cell culture studies showed that PGE 2 counteracts AVP action by enhancing AQP2 endocytotic uptake from the apical plasma membrane (33). On the other hand, recent studies showed that inhibition of COX by indomethacin reduced renal AQP2 expression in rats, implying that PGs may actually help maintain AQP2 levels (20).In addition to the well-known renal effects of PGs on urine concentration, other evidence suggests that COX-derived products could influence this process by acting at central locales. Early studies showed that AVP release was stimulated by PGE 2 in the rat neurohypophysis (32). Ishikawa et al. (17) showed a reduced release of AVP in response to either hyperosmotic exposure or ANG II in guinea pig hypothalamoneurohypophyseal cultures following treatment with indomethacin. Finally, an intracerebroventri...

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Prostaglandin E2 inhibits sodium transport in rabbit cortical collecting duct by increasing intracellular calcium.

Cited by 123 publications

References 37 publications

Involvement of EP1 and EP2 receptors in the regulation of the Na,K-ATPase by prostaglandins in MDCK cells

Involvement of EP1 and EP2 receptors in the regulation of the Na,K-ATPase by prostaglandins in MDCK cells

EP₁‐ and FP‐mediated cross‐desensitization of the alpha (α) and beta (β) isoforms of the human thromboxane A₂ receptor

Urine concentrating defect in prostaglandin EP₁-deficient mice

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Prostaglandin E2 inhibits sodium transport in rabbit cortical collecting duct by increasing intracellular calcium.

Cited by 123 publications

References 37 publications

Involvement of EP1 and EP2 receptors in the regulation of the Na,K-ATPase by prostaglandins in MDCK cells

Involvement of EP1 and EP2 receptors in the regulation of the Na,K-ATPase by prostaglandins in MDCK cells

EP1‐ and FP‐mediated cross‐desensitization of the alpha (α) and beta (β) isoforms of the human thromboxane A2 receptor

Urine concentrating defect in prostaglandin EP1-deficient mice

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EP₁‐ and FP‐mediated cross‐desensitization of the alpha (α) and beta (β) isoforms of the human thromboxane A₂ receptor

Urine concentrating defect in prostaglandin EP₁-deficient mice