Search Results

August 2022 Dopamine D 1 receptor-mediated β-arrestin signaling: Insight from pharmacology, biology,

precursors and 48 putative neuropeptide G protein-coupled receptor (GPCR) genes were identified in D. research provides more knowledge on neuropeptide systems and sets the groundwork for the creation of novel D.

Alterations in the expression and/or activity of brain G-protein-coupled receptors (GPCRs) such as dopamine D1R, D2LR, D3R, and D4R, vasopressin V1AR, and serotonin 5-HT1AR are noted in various neurodegenerative diseases (NDDs). Since studies have indicated that flavonoids can target brain GPCRs and provide neuroprotection via inhibition of monoamine oxidases (hMAOs), our study explored the functional role of kurarinone, an abundant lavandulated flavonoid in Sophora flavescens, on dopamine receptor subtypes, V1AR, 5-HT1AR, and hMAOs. Radioligand binding assays revealed considerable binding of kurarinone on D1R, D2LR, and D4R. Functional GPCR assays unfolded the compound's antagonist behavior on D1R (IC50 42.1 ± 0.35 μM) and agonist effect on D2LR and D4R (EC50 22.4 ± 3.46 and 71.3 ± 4.94 μM, respectively). Kurarinone was found to inhibit hMAO isoenzymes in a modest and nonspecific manner. Molecular docking displayed low binding energies during the intermolecular interactions of kurarinone with the key residues of the deep orthosteric binding pocket and the extracellular loops of D1R, D2LR, and D4R, validating substantial binding affinities to these prime targets. With appreciable D2LR and D4R agonism and D1R antagonism, kurarinone might be a potential compound that can alleviate clinical symptoms of Parkinson's disease and other NDDs. Read full article

This Week’s Highlights: G protein-coupled receptor (GPCR) pharmacogenomics Miles D Thompson , David delivery of liposome encapsulated flavonoids ameliorates l-DOPA induced dyskinesia in hemiparkinsonian mice

October 2022 Increased Anxiety-like Behaviors in Adgra1-/- Male But Not Female Mice are Attributable We found that Adgra1-/- male but not female mice exhibited elevated anxiety levels in the open field, mice. Finally, we found that PI3K/AKT/GSK-3β and MEK/ERK in amygdalae of Adgra1-deficient male mice were aberrantly activated when compared to wt male mice.

October 2022 High hedgehog signaling is transduced by a multikinase-dependent switch controlling the apico-basal distribution of the GPCR smoothened "The oncogenic G-protein-coupled receptor (GPCR) Smoothened (SMO) is a key transducer of the hedgehog (HH) morphogen, which plays an essential role in the patterning of epithelial structures. Here, we examine how HH controls SMO subcellular localization and activity in a polarized epithelium using the Drosophila wing imaginal disc as a model. We provide evidence that HH promotes the stabilization of SMO by switching its fate after endocytosis toward recycling. This effect involves the sequential and additive action of protein kinase A, casein kinase I, and the Fused (FU) kinase. Moreover, in the presence of very high levels of HH, the second effect of FU leads to the local enrichment of SMO in the most basal domain of the cell membrane. Together, these results link the morphogenetic effects of HH to the apico-basal distribution of SMO and provide a novel mechanism for the regulation of a GPCR." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 Angiotensin-(1-7) improves cognitive function and reduces inflammation in mice following mild traumatic brain injury "Traumatic brain injury (TBI) is a leading cause of disability in the US study examined the therapeutic effect of Ang-(1-7) on secondary injury observed in a murine model of mild

September 2022 "The G-protein-coupled bile acid receptor, Gpbar1 or TGR5, is characterized as a membrane receptor specifically activated by bile acids.

The present study aims to investigate the possible role of FSH excess in male bone health, by comparing

The resulting homozygous hPTH1R-KI (humanized) mice were healthy over at least 10 generations and showed The initial evaluation of these mice and their potential utility for predicting behavior of PTH analogues

involves alveolar differentiation of mammary epithelial cells (MECs), which is essential for breast milk assessing changes in cellular viability, lipid accumulation, and gene and protein expression of major milk We hypothesized that THC and CBD will negatively impact the synthesis of milk proteins and lipids, as Relative to control, 10μM THC and 10μM CBD reduced mRNA levels of milk proteins (CSN2 and WAP), lipid

mice. and female mice. DOI elicited more HTR in female as compared to male C57BL/6J mice, a sex-specific exacerbated behavior C57BL/6J mice. C57BL/6J mice.

We have cloned and characterized SK and SKR genes in the D. armandi and carried out bioinformatics predictions The expression levels of the two genes were different between male and female adults, and there were parallel, injection of SK caused a significant reduction in body weight and increase in mortality of D.

This week's highlight includes congrats to: Miles Thompson , Alexander Hauser , Caroline Gorvin ,   et

., Strader, D. J., Benovic, J. L., Dohlman, H. G., Frielle, T., Bolanowski, M. A., Bennett, C. D., Rands, E., Diehl, R. E., Mumford, R. A., Slater, E. E., Sigal, I. S., Caron, M. D. (1986). B., Panova, O., Hilger, D., Casiraghi, M., He, F., Maul, L., Gmeiner, P., Kobilka, B.

Miles Thompson, Alexander Hauser, Caroline Gorvin et al. for their research on GPCR gene variants and

., & Fowler, D. M. (2011). Deep mutational scanning: assessing protein function on a massive scale. Trends in Biotechnology , 29 (9), 435–442. https://doi.org/10.1016/j.tibtech.2011.04.003 Fowler, D. M., Trinidad, D. D., English, J. G., Coyote-Maestas, W., & Aashish Manglik. (2024).

., Rosenbaum, D. M., Thian, F. S., Kobilka, T. S., Schnapp, A., Konetzki, I., Sunahara, R. N., Angelini, A., Waghray, D., Dror, R. O., Ploegh, H. L., & Garcia, K. C. (2015). Science (New York, N.Y.), 347(6226), 1113–1117. https://doi.org/10.1126/science.aaa5026 Wu, A., Salom, D. D., Tworak, A., Watanabe, K., Pardon, E., Steyaert, J., Kandori, H., Katayama, K., Kiser, P. D., & Palczewski, K. (2023).

characteristics with the 2 cases we previously reported as follows: (a) elderly (74-87 years at diagnosis), (b) male , (c) unexpectedly showed no other autoimmune diseases, (d) showed spontaneously fluctuating Ca levels

This week's highlight includes congrats to: Miles Thompson ,   Alexander Hauser ,   Caroline Gorvin ,

D., & Collins, B. M. (2019). J., & Calebiro, D. (2016). Endocrinology, 157(4), 1613–1621. https://doi.org/10.1210/en.2015-1945 Irannejad, R., Pessino, V., Mika, D. J., & Calebiro, D. (2017). Z., Wilderman, A., Katakia, T., McCann, T., Yokouchi, H., Zhang, L., Corriden, R., Liu, D., Feigin, M

Fowler, D. M., & Fields, S. (2014). Deep mutational scanning: a new style of protein science. C., Sykes, D. A., Viray, A. E., Vitale, R. M., Tomašević, N., ... & Carreira, E. M. (2024). D., Muñoz, L. L., Gregory, K. J., White, P. J., Sexton, P. M., Christopoulos, A., & May, L.

Allosteric Modulator. α1-adrenoceptor ligands inhibit chemokine receptor heteromerization partners of α1B/D-adrenoceptors A small molecule ligand for the novel pain target, GPR171, produces minimal reward in mice. Endogenous l- to d-amino acid residue isomerization modulates selectivity between distinct neuropeptide

currents GPCR Binders, Drugs, and more LP2, a cyclic angiotensin-(1-7) analog extended with an N-terminal D-lysine , impairs growth of patient-derived xenografts of colorectal carcinoma in mice Methods & Updates in GPCR

Phylogenetic comparison of GPCRs in D. celebensis to those in humans (Homo sapiens), fruitfly (Drosophila Our findings suggest sporadic evolutionary processes within the GPCR gene families identified in D. celebensis

from more than 60 ORs in the testis and only a few ORs in the liver (Flegel C. et al. 2013; Maßberg D. ORs, although there are highly increased in prostate tissue, especially in prostate cancer (Maßberg D. sandalore-activated receptor OR2AT4 shown to promote human keratinocyte proliferation and migration (Busse D. olfactory-specific chaperones to be correctly targeted to the surface of heterologous cells (Maßberg D.

Improving Hematopoietic Stem Cell Mobilization Using Propranolol with GPC-100 Sosei Heptares to Host R&D Day Highlighting its Innovative R&D and Late-Stage Development Progress Parker Moss to Join Exscientia

Multi-target Collaboration and License Agreement in Diabetes and Metabolic Diseases Sosei Heptares Enters R&D Treating Type 2 Diabetes and Obesity Special report 2022: Meet 20 women blazing trails in biopharma R&D