Vasodilatory effects of the selective GPER agonist G-1 is maximal in arteries of postmenopausal women

Arefin, Samsul; Simoncini, Tommaso; Wieland, Rebekah; Hammarqvist, Folke; Spina, Stefania; Goglia, Lorenzo; Kublickiene, Karolina

doi:10.1016/j.maturitas.2014.04.002

Cited by 40 publications

(25 citation statements)

References 39 publications

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“…The signaling mechanism(s) of GPER‐dependent activation of nNOS pathway is unknown. Interestingly, in line with our observations, in the vasculature G‐1 can also induce NO release from endothelial cells via the endothelial eNOS pathway, leading to vasodilatations . It is known that nNOS is Ca 2+ ‐ and calmodulin‐dependent enzyme, which is inactive at an intracellular Ca 2+ concentration below 100 nmol/L, and is fully activated at [Ca 2+ ] of 500 nmol/L .…”

Section: Discussionsupporting

confidence: 89%

“…Interestingly, in line with our observations, in the vasculature G-1 can also induce NO release from endothelial cells via the endothelial eNOS pathway, leading to vasodilatations. 54,55 It is known that nNOS is Ca 2+ -and calmodulin-dependent enzyme, 56,57 which is inactive at an intracellular Ca 2+ concentration below 100 nmol/L, and is fully activated at [Ca 2+ ] of 500 nmol/L. 58 This range of [Ca 2+ ] is in accordance with changes in intracellular Ca 2+ concentrations upon excitatory activation in neuronal cells.…”

Section: Discussionmentioning

confidence: 83%

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G protein‐coupled estrogen receptor is involved in modulating colonic motor function via nitric oxide release in C57BL/6 female mice

Jiang

et al. 2015

Neurogastroenterology Motil

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 83%

G protein‐coupled estrogen receptor is involved in modulating colonic motor function via nitric oxide release in C57BL/6 female mice

Jiang

et al. 2015

Neurogastroenterology Motil

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“…Arterial segmentation and vascular reactivity studies were carried out as previously described (Arefin et al, ). Briefly, the subcutaneous fat biopsies were obtained from the lower abdomen from healthy donors and placed in cold physiological salt solution (PSS: NaCl 119 mM, KCl 4.7 mM, CaCl 2 2.5 mM, MgSO 4 1.17 mM, NaHCO 3 25 mM, KH 2 PO 4 1.18 mM, EDTA 0.026 mM, and glucose 5.5 mM).…”

Section: Methodsmentioning

confidence: 99%

Biological characterization of new inhibitors of microsomal PGE synthase‐1 in preclinical models of inflammation and vascular tone

Larsson

Steinmetz

Bergqvist

et al. 2019

British J Pharmacology

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Background and Purpose: Microsomal PGE synthase-1 (mPGES-1), the inducible synthase that catalyses the terminal step in PGE 2 biosynthesis, is of high interest as therapeutic target to treat inflammation. Inhibition of mPGES-1 is suggested to be safer than traditional NSAIDs, and recent data demonstrate anti-constrictive effects on vascular tone, indicating new therapeutic opportunities. However, there is a lack of potent mPGES-1 inhibitors lacking interspecies differences for conducting in vivo studies in relevant preclinical disease models.Experimental Approach: Potency was determined based on the reduction of PGE 2 formation in recombinant enzyme assays, cellular assay, human whole blood assay, and air pouch mouse model. Anti-inflammatory properties were assessed by acute paw swelling in a paw oedema rat model. Effect on vascular tone was determined with human ex vivo wire myography. Key Results:We report five new mPGES-1 inhibitors (named 934, 117, 118, 322, and 323) that selectively inhibit recombinant human and rat mPGES-1 with IC 50 values of 10-29 and 67-250 nM respectively. The compounds inhibited PGE 2 production in a cellular assay (IC 50 values 0.15-0.82 μM) and in a human whole blood assay (IC 50 values 3.3-8.7 μM). Moreover, the compounds blocked PGE 2 formation in an air pouch mouse model and reduced acute paw swelling in a paw oedema rat model. Human ex vivo wire myography analysis showed reduced adrenergic vasoconstriction after incubation with the compounds. Conclusion and Implications:These mPGES-1 inhibitors can be used as refined tools in further investigations of the role of mPGES-1 in inflammation and microvascular disease.

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“…These differing signaling pathways for GPER may result from alterations in smooth muscle versus endothelial expression levels of the receptor, which differ according to vascular bed (39). Regardless, the ability of GPER to directly induce vasodilation is well-established in animal models as well as in human arteries (40, 41). …”

Section: Hypertension and Kidney Diseasementioning

confidence: 99%

GPER–novel membrane oestrogen receptor

et al. 2016

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The recent discovery of the G protein-coupled estrogen receptor (GPER) presents new challenges and opportunities for understanding the physiology, pathophysiology, and pharmacology of many diseases. This review will focus on the expression and function of GPER in hypertension, kidney disease, atherosclerosis, vascular remodeling, heart failure, reproduction, metabolic disorders, cancer, environmental health, and menopause. Furthermore, this review will highlight the potential of GPER as a therapeutic target.

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Vasodilatory effects of the selective GPER agonist G-1 is maximal in arteries of postmenopausal women

Cited by 40 publications

References 39 publications

G protein‐coupled estrogen receptor is involved in modulating colonic motor function via nitric oxide release in C57BL/6 female mice

G protein‐coupled estrogen receptor is involved in modulating colonic motor function via nitric oxide release in C57BL/6 female mice

Biological characterization of new inhibitors of microsomal PGE synthase‐1 in preclinical models of inflammation and vascular tone

GPER–novel membrane oestrogen receptor

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