RGS proteins and cardiovascular Angiotensin II Signaling: Novel opportunities for therapeutic targeting

Lymperopoulos, Anastasios; Borges, Jordana I.; Stoicovy, Renee A.

doi:10.1016/j.bcp.2023.115904

Cited by 9 publications

(3 citation statements)

References 76 publications

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“…Another likely regulatory mechanism is G protein signaling (RGS) proteins, which negatively regulate G protein-coupled receptors [ 46 ]. Certain RGS proteins, specifically RGS2 and RGS4, are known to regulate adrenal aldosterone synthesis in response to angiotensin II [ 47 ], and at least RGS2 has been reported to be suppressed by estrogen [ 48 ]. Given that AT 1 R-GPER interferes in the synthesis of aldosterone [ 49 ], it is quite plausible that RGS proteins are also involved in the effects of estrogens on adrenocortical aldosterone production.…”

Section: Molecular Evidence Of Estrogens In the Biosynthesis Of Aldos...mentioning

confidence: 99%

The role of sex hormones in aldosterone biosynthesis and their potential impact on its mineralocorticoid receptor

Vecchiola,

Uslar,

Friedrich

et al. 2024

Cardiovascular Endocrinology &Amp; Metabolism

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Blood pressure (BP) regulation is a complex process involving various hormones, including aldosterone and its mineralocorticoid receptor. Mineralocorticoid receptor is expressed in several tissues, including the kidney, and plays a crucial role in regulating BP by controlling the sodium and water balance. During different stages of life, hormonal changes can affect mineralocorticoid receptor activity and aldosterone levels, leading to changes in BP. Increasing evidence suggests that sex steroids modulate aldosterone levels. Estrogens, particularly estradiol, mediate aldosterone biosynthesis by activating classical estrogen receptors and the G protein-coupled receptor. Progesterone acts as an anti-mineralocorticoid by inhibiting the binding of aldosterone to the mineralocorticoid receptor. Moreover, progesterone inhibits aldosterone synthase enzymes. The effect of testosterone on aldosterone synthesis is still a subject of debate. However, certain studies show that testosterone downregulates the mRNA levels of aldosterone synthase, leading to decreased plasma aldosterone levels.

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Section: Molecular Evidence Of Estrogens In the Biosynthesis Of Aldos...mentioning

confidence: 99%

The role of sex hormones in aldosterone biosynthesis and their potential impact on its mineralocorticoid receptor

Vecchiola,

Uslar,

Friedrich

et al. 2024

Cardiovascular Endocrinology &Amp; Metabolism

View full text Add to dashboard Cite

show abstract

“…Interestingly, a recent study documented a novel molecular target for dapagliflozin's sympatholytic effects: the adrenal Regulator of G protein Signaling (RGS)-4 upregulation [14]. RGS4 belongs to the superfamily of GTPase-activating proteins (GAPs) for G proteins; i.e., it accelerates G i/o -and G q/11 -protein-signaling termination [15]. RGS4 is abundantly expressed in the adrenal glands, both in the cortex and in the medulla [16], and its genetic deletion in mice is associated with elevated levels of circulating catecholamines, i.e., increased sympathetic activity, and elevated free fatty acid (FFA) levels in the blood [17].…”

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confidence: 99%

“…Of note, one of the four G-protein-coupled receptors (GPCRs) mediating FFA signaling inside cells [18], FFA receptor type 3 (FFAR3), has been reported to promote norepinephrine release from sympathetic neurons [19], and FFAR3 signaling was recently shown to be inhibited by RGS4 in cardiomyocytes and sympathetic-like neurons [20]. In any case, adrenal RGS4 inhibits cholinergic (vagal)-nerve-stimulated catecholamine release from the chromaffin cells of the adrenal medulla [15,17], making it sympatholytic in this secretory organ. Consequently, dapagliflozin, by transcriptionally upregulating RGS4 in the adrenals [14], can have a direct sympatholytic effect via RGS4 in the adrenal medulla.…”

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confidence: 99%