Showing items related by title, author, creator and subject.

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  THE CONCISE GUIDE TO PHARMACOLOGY 2021/22 : G protein-coupled receptors 

  Alexander, Stephen P. H.; Kukkonen, Jyrki P. (2021)

  The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at . G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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  The angiotensin receptor 2 agonist, compound 21, facilitates TRKB activation and reduces the consequences of stress in mice 

  Laukkanen, Liina (Helsingin yliopisto, 2021)

  This study investigated the in vitro and in vivo effects of direct angiotensin II (ANG) receptor type 2 (AGTR2) agonist Compound 21 (C21). The blockade of ANG receptor type 1 (AGTR1) by AGTR1 antagonists has long been associated with antidepressant and anxiolytic effects. Furthermore, it has been suggested that the therapeutic effects of the AGTR1 antagonists are partially dependent on enhancing the signaling through neuroprotective AGTR2. This suggests that as a specific AGTR2 agonist C21 could be used as a potential therapeutic tool to treat mood disorders that would greatly benefit from new effective treatments. Brain-derived neurotrophic factor (BDNF) is a neurotrophic that binds to tropomyosin receptor kinase B (TRKB). This study aimed to test how C21 affects BDNF:TRKB signaling that has been shown to regulate the therapeutic effects of different antidepressants that act on mood disorders. In vitro effects of C21 on BDNF:TRKB signaling were investigated with ELISA in the cortical cell cultures. Acute AGTR2 stimulation significantly elevated the amount of surface TRKB whereas a prolonged treatment of C21 for three consecutive days induced activation of TRKB. Similarly, combined treatment of C21 and a non-therapeutic treatment of BDNF induced TRKB activation, further linking the AGTR2 stimulation by this compound to the BDNF:TRKB signaling. In vivo effects of C21 on conditioned and unconditioned fear were investigated in mice by using contextual fear conditioning and elevated plus-maze (EPM) respectively. The therapeutic effect of C21 protected mice from conditioned fear but failed to provide similar results for unconditioned fear in the EPM. Interestingly, these stress-protective effects of AGTR2 stimulation were lost in the BDNF-deficient animals. To conclude, AGTR2 stimulation by C21 elevates the amount of surface TRKB that enhances the BDNF:TRKB signaling similar to antidepressants, which further leads to the therapeutic, stress-protective effects. Furthermore, these AGTR2-induced effects were absent without exposure to stress or when BDNF was diminished, indicating that both fear conditioning and BDNF are crucially involved. This study suggests that the AGTR2 is indeed a potential therapeutic target for treating mood disorders, and that in the future C21 could be translated for this use. To achieve this result, the cell types that regulate this effect need to be identified.
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  Expression of hormone receptors in oropharyngeal squamous cell carcinoma 

  Mohamed, Hesham; Aro, Katri; Jouhi, Lauri; Makitie, Antti; Remes, Satu; Haglund, Caj; Atula, Timo; Hagstrom, Jaana (2018)

  Hormone receptors play an important role in many types of cancers. Alongside factors associated with human papillomavirus (HPV) infection, hormonal receptors may impact the tumorigenesis of oropharyngeal cancer. This study consists of 199 consecutive oropharyngeal squamous cell carcinoma (OPSCC) patients diagnosed and treated with a curative intent. We examined androgen (AR), estrogen (ER; both alpha and beta), and progesterone receptor (PR) expressions using immunohistochemistry comparing tumor and patient characteristics. AR was expressed in 16%, PR in 27% and ER-beta in 63% of the tumors. HPV- and p16-positive tumors expressed more AR and less PR than their negative counterparts. High PR expression was associated with poor disease-specific and locoregional recurrence-free survival. AR, PR, and ER-beta are expressed in OPSCC, and AR and PR expressions are associated with HPV and p16 status. Furthermore, PR appears to have prognostic significance. This may allow us to investigate the role of anti-hormone receptors in the treatment of OPSCC.