ArticleAmerican journal of physiology. Renal physiology2011
A major role for the EP4 receptor in regulation of renin.
Article in American journal of physiology. Renal physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 44 citations in OpenAlex.
- Crosstalk between renin and arachidonic acid (and its metabolites).Lipids in health and disease · 2025Review
- Cell-Specific Actions of the Prostaglandin E-Prostanoid Receptor 4 Attenuating Hypertension: A Dominant Role for Kidney Epithelial Cells Compared With Macrophages.Journal of the American Heart Association · 2022Article
- Flexible and multifaceted: the plasticity of renin-expressing cells.Pflugers Archiv : European journal of physiology · 2022Review
- NaHypertension (Dallas, Tex. : 1979) · 2022Article
- Review
- Roles of EP Receptors in the Regulation of Fluid Balance and Blood Pressure.Frontiers in endocrinology · 2022Review
- Endothelial cell prostaglandin E2 receptor EP4 is essential for blood pressure homeostasis.JCI insight · 2020Article
- Role of protease-activated receptor 2 in regulation of renin synthesis and secretion in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2019Article
- Complex Role for E-Prostanoid 4 Receptors in Hypertension.Journal of the American Heart Association · 2019Article
- Autocrine-paracrine prostaglandin ENature immunology · 2018Article
- COX-2-derived PGEPflugers Archiv : European journal of physiology · 2018Article
- The renin-angiotensin-aldosterone system and calcium-regulatory hormones.Journal of human hypertension · 2015Review
- Salt restriction leads to activation of adult renal mesenchymal stromal cell-like cells via prostaglandin E2 and E-prostanoid receptor 4.Hypertension (Dallas, Tex. : 1979) · 2015Article
- Crosstalk between (Pro)renin receptor and COX-2 in the renal medulla during angiotensin II-induced hypertension.Current opinion in pharmacology · 2015Review
- Prostaglandin E-prostanoid4 receptor mediates angiotensin II-induced (pro)renin receptor expression in the rat renal medulla.Hypertension (Dallas, Tex. : 1979) · 2014Article
- Classical Renin-Angiotensin system in kidney physiology.Comprehensive Physiology · 2014Review
- Direct regulation of ENaC by bradykinin in the distal nephron. Implications for renal sodium handling.Current opinion in nephrology and hypertension · 2014Review
- Vitamin D increases plasma renin activity independently of plasma Ca2+ via hypovolemia and β-adrenergic activity.American journal of physiology. Renal physiology · 2013Article
- E-type prostanoid receptor 4 (EP4) in disease and therapy.Pharmacology & therapeutics · 2013Review
- The influence of extracellular and intracellular calcium on the secretion of renin.Pflugers Archiv : European journal of physiology · 2013Review
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
Prostaglandins have been implicated as paracrine regulators of renin secretion, but the specific pathways and receptor(s) carrying out these functions have not been fully elucidated. To examine the contributions of prostanoid synthetic pathways and receptors to regulation of renin in the intact animal, we used a panel of mice with targeted disruption of several key genes: cyclooxygenase-2 (COX-2), microsomal PGE synthases 1 and 2 (mPGES1, mPGES2), EP2 and EP4 receptors for PGE(2), and the IP receptor for PGI(2). To activate the macula densa signal for renin stimulation, mice were treated with furosemide over 5 days and renin mRNA levels were determined by real-time RT-PCR. At baseline, there were no differences in renin mRNA levels between wild-type and the various strains of mutant mice. Furosemide caused marked stimulation of renin mRNA expression across all groups of wild-type control mice. This response was completely abrogated in the absence of COX-2, but was unaffected in mice lacking mPGES1 or mPGES2. The absence of G(s)/cAMP-linked EP2 receptors had no effect on stimulation of renin by furosemide and there was only a modest, insignificant reduction in renin responses in mice lacking the IP receptor. By contrast, renin stimulation in EP4(-/-) mice was significantly reduced by ∼70% compared with wild-type controls. These data suggest that stimulation of renin by the macula densa mechanism is mediated by PGE(2) through a pathway requiring COX-2 and the EP4 receptor, but not EP2 or IP receptors. Surprisingly, mPGES1 or mPGES2 are not required, suggesting other alternative mechanisms for generating PGE(2) in response to macula densa stimulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.