ArticleEuropean journal of pharmacology2014
2-methoxyestradiol binding of GPR30 down-regulates angiotensin AT(1) receptor.
Article in European journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Sex- and site-specific effects of GPER-1 activation on saccharin vs cocaine preference in male and female rats.Hormones and behavior · 2025Article
- Decoding the enigmatic estrogen paradox in pulmonary hypertension: delving into estrogen metabolites and metabolic enzymes.Cellular & molecular biology letters · 2024Review
- Hormonal influence: unraveling the impact of sex hormones on vascular smooth muscle cells.Biological research · 2024Review
- The Role of G Protein-Coupled Estrogen Receptor (GPER) in Vascular Pathology and Physiology.Biomolecules · 2023Review
- The G protein-coupled oestrogen receptor GPER in health and disease: an update.Nature reviews. Endocrinology · 2023Review
- G Protein-Coupled Estrogen Receptor GPER: Molecular Pharmacology and Therapeutic Applications.Annual review of pharmacology and toxicology · 2023Review
- Effects of 2-Methoxyestradiol, a Main Metabolite of Estradiol on Hepatic ABCA1 Expression in HepG2 Cells.Nutrients · 2022Article
- Estrogen Metabolite 2-Methoxyestradiol Attenuates Blood Pressure in Hypertensive Rats by Downregulating Angiotensin Type 1 Receptor.Frontiers in physiology · 2022Article
- Endometriosis-Associated Angiogenesis and Anti-angiogenic Therapy for Endometriosis.Frontiers in global women's health · 2022Review
- Article
- Sex Differences, Estrogen Metabolism and Signaling in the Development of Pulmonary Arterial Hypertension.Frontiers in cardiovascular medicine · 2021Review
- Central CYP1B1 (Cytochrome P450 1B1)-Estradiol Metabolite 2-Methoxyestradiol Protects From Hypertension and Neuroinflammation in Female Mice.Hypertension (Dallas, Tex. : 1979) · 2020Article
- Estradiol Metabolism: Crossroads in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2019Review
- 2-Methoxyestradiol Attenuates Angiotensin II-Induced Hypertension, Cardiovascular Remodeling, and Renal Injury.Journal of cardiovascular pharmacology · 2019Article
- G Protein-Coupled Estrogen Receptor 1 Inhibits Angiotensin II-Induced Cardiomyocyte Hypertrophy via the Regulation of PI3K-Akt-mTOR Signalling and Autophagy.International journal of biological sciences · 2019Article
- GPCRs in context: sexual dimorphism in the cardiovascular system.British journal of pharmacology · 2018Review
- Molecular pathways of oestrogen receptors and β-adrenergic receptors in cardiac cells: Recognition of their similarities, interactions and therapeutic value.Acta physiologica (Oxford, England) · 2018Review
- 2-Methoxyestradiol, an endogenous 17β-estradiol metabolite, inhibits microglial proliferation and activation via an estrogen receptor-independent mechanism.American journal of physiology. Endocrinology and metabolism · 2016Article
- GPR30 decreases with vascular aging and promotes vascular smooth muscle cells maintaining differentiated phenotype and suppressing migration via activation of ERK1/2.OncoTargets and therapy · 2016Article
- International Union of Basic and Clinical Pharmacology. XCVII. G Protein-Coupled Estrogen Receptor and Its Pharmacologic Modulators.Pharmacological reviews · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Controlling angiotensin AT1 receptor function has been shown to be protective for many pathophysiological disorders. Although estrogen metabolite, 2-methoxyestradiol (2ME2) can down-regulate angiotensin AT1 receptor expression independently of nuclear receptors, no specific cellular targets have been identified. This study was focused on identification and validation of a cellular target responsible for 2ME2-mediated angiotensin AT1 receptor down-regulation in a continuously passaged rat liver epithelial cell line. Cell membranes were isolated and used to determine 2ME2 specific binding. Cell membranes exposed to [(3)H]2ME2 showed specific saturable binding, which was found to be pertussis toxin (PTx) sensitive. Under similar conditions, G-protein coupled receptor 30 (GPR30) agonist (G1) and antagonist (G15) inhibited 2ME2 specific binding. In these cells GPR30 was found localized to endoplasmic reticulum (ER) membranes. In intact cells, G1 down-regulated angiotensin AT1 receptor expression and this effect was reversed by G15. Furthermore, 2ME2 mediated activation of epidermal growth factor receptor (EGFR) followed by ERK1/2 phosphorylation, an essential signaling step in angiotensin AT1 receptor down-regulation, was abrogated by G15, suggesting that this signal is GPR30 dependent. Additionally, EGF was found to independently down-regulate angiotensin AT1 receptor in an ERK1/2-dependent manner. In summary, our results demonstrate for the first time that 2ME2 down-regulation of angiotensin AT1 receptor is dependent on ER membrane-associated GRP30. Moreover, this effect is facilitated by GPR30 dependent transactivation of EGFR and ERK1/2 phosphorylation. This study provides further understanding of the physiological significance of 2ME2 and its role in modulating angiotensin AT1 receptor expression.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.