Last update 01 Nov 2024

ADRA1 x GR

Last update 01 Nov 2024

Basic Info

Related Targets

ADRA1GR

Drugs associated with ADRA1 x GR

Prednisolone/Tetrahydrozoline Hydrochloride

Target

ADRA1 x GR

Mechanism

ADRA1 agonists [+1]

Active Org.

Yoshindo, Inc.

Originator Org.

Yoshindo, Inc.

Active Indication

Nasal Obstruction

Inactive Indication-

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date27 Jul 1964

Hydrocodone Bitartrate/Phenylpropanolamine Hydrochloride

Target

ADRA1 x D1 receptor x GR x α2A-AR x β1-adrenergic receptor x β2-adrenergic receptor

Mechanism

ADRA1 agonists [+5]

Active Org.-

Originator Org.-

Active Indication

Cough [+1]

Inactive Indication-

Drug Highest PhaseApproved

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Mometasone furoate/Oxymetazoline Hydrochloride

Target

GR x α1A-AR

Mechanism

GR agonists [+1]

Active Org.-

Originator Org.

Merck & Co., Inc.

Active Indication-

Inactive Indication

Rhinitis, Allergic, Seasonal

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with ADRA1 x GR

100 Translational Medicine associated with ADRA1 x GR

0 Patents (Medical) associated with ADRA1 x GR

Literatures (Medical) associated with ADRA1 x GR

01 Feb 2024·Psychosomatic Medicine

Glucocorticoid and Adrenergic Receptor Distribution Across Human Organs and Tissues: A Map for Stress Transduction

Article

Author: Basarrate, Sophia ; Trumpff, Caroline ; Marsland, Anna L ; Picard, Martin ; Monzel, Anna S ; Smith, Janell L M

ABSTRACTObjectivePsychosocial stress is transduced into disease risk through energy-dependent release of hormones from the hypothalamic-pituitary-adrenal and sympathetic-adrenal-medullary axes. The levels of glucocorticoid and adrenergic hormones, together with the sensitivity of tissues to their signaling, define stress responses. To understand existing pathways responsible for the psychobiological transduction of stressful experiences, we provide a quantitative whole-body map of glucocorticoid and adrenergic receptor (AR) expression.MethodsWe systematically examined gene expression levels for the glucocorticoid receptor (GR), α- and β-ARs (AR-α1B, AR-α2B AR-β2, and AR-β3), across 55 different organs using the Human Protein Atlas and Human Proteome Map datasets. Given that mitochondria produce the energy required to respond to stress, we leveraged the Human Protein Atlas and MitoCarta3.0 data to examine the link between stress hormone receptor density and mitochondrial gene expression. Finally, we tested the functional interplay between GR activation and AR expression in human fibroblast cells.ResultsThe GR was expressed ubiquitously across all investigated organ systems, whereas AR subtypes showed lower and more localized expression patterns. Receptor co-regulation, meaning the correlated gene expression of multiple stress hormone receptors, was found between GR and AR-α1B, as well as between AR-α1B and AR-α2B. In cultured human fibroblasts, activating the GR selectively increased AR-β2 and AR-α1B expression. Consistent with the known energetic cost of stress responses, GR and AR expressions were positively associated with the expression of specific mitochondrial pathways.ConclusionsOur results provide a cartography of GR and AR expression across the human body. Because stress-induced GR and AR signaling triggers energetically expensive cellular pathways involving energy-transforming mitochondria, the tissue-specific expression and co-expression patterns of hormone receptor subtypes may in part determine the resilience or vulnerability of different organ systems.

01 Apr 2023·Protein Science

Study of novel androgen receptor V770 variant in androgen insensitivity syndrome patients reveals the transitional state of the androgen receptor ligand binding domain homodimer

Article

Author: Lee, Xiao Yin ; Giagulli, Vito ; Helsen, Christine ; Claessens, Frank ; Eerlings, Roy ; Vinanzi, Cinzia ; De Block, Sofie ; Voet, Arnout ; Ferlin, Alberto ; Nguyen, Tien T. ; Di Millo, Francesco ; Rocca, Maria Santa

AbstractWe report the discovery of the androgen receptor missense mutation V770D, that was found in two sisters suffering from complete androgen insensitivity. Experimental validation of AR V770 variants demonstrated that AR V770D was transcriptionally inactive due to the inability to dimerize and a reduced ligand binding affinity. The more conservative AR V770A variant showed a dimerization defect at low levels of DHT with a partial recovery of the transcriptional activity and of the receptor's ability to dimerize when increasing the DHT levels. With V770 located outside of the proposed LBD dimerization interface of the AR LBD homodimer crystal structure, the effects of the V770A mutation on AR dimerization were unexpected. We therefore explored whether the AR LBD dimerization interface would be better described by an alternative dimerization mode based on available human homodimeric LBD crystal structures of other nuclear receptors. Superposition of the monomeric AR LBD in the homodimeric crystal structures of GR, PR, ER, CAR, TRβ, and HNF‐4α showed that the GR‐like LBD dimer model was energetically the most stable. Moreover, V770 was a key energy residue in the GR‐like LBD dimer while it was not involved in the stabilization of the AR LBD homodimer according to the crystal structure. Additionally, the observation that 4 AIS mutations impacted the stability of the AR LBD dimer while 16 mutations affected the GR‐like LBD dimer, suggested that the AR LBD dimer crystal is a snapshot of a breathing AR LBD homodimer that can transition into the GR‐like LBD dimer model.

01 Feb 2021·Bulletin of Experimental Biology and MedicineQ4 · MEDICINE

Influence of Social Isolation Stress on Age-Related Changes in Functional Activity and Expression of Receptors of Endogenous Vasoconstrictors in Rat Aorta

Q4 · MEDICINE

Article

Author: Kryzhanovskii, S A ; Tsorin, I B ; Sukhanova, I F ; Kozhevnikova, L M ; Vititnova, M B

Social isolation stress was modeled by long-term isolation of 12-month-old rats in individual cages over 28 weeks. It was found that sensitization of blood vessels to the vasoconstrictor action of serotonin due to overexpression of 5HT2A-type receptor genes, as well as an imbalance in the expression level of endothelin ETA- and ETB-receptors (55 and 153%, respectively) are the early signs of vascular aging. A significant contribution to the development of age-related changes in the contractile properties of blood vessels is made by the stress component, which is manifested at the level of glucocorticoid-dependent mechanisms of regulation of gene expression. The decrease in the expression of glucocorticoid receptors caused by isolation stress leads to a decrease in the expression of the genes responsible for the synthesis of V1A-R and ATII-R and to the development of vascular hyporeactivity to the vasoconstrictor action of ATII and AVP. In the aorta of stressed rats, the α1-AR mRNA level increases by 3 times. At the same time, stress did not affect the dynamics of age-related changes in the expression of genes encoding 5HT2A-R and ETA/ETB-R.

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