Article
Pharmacology & Pharmacy
Michael W. Rudokas, John P. Post, Alejandra Sataray-Rodriguez, Rinzhin T. Sherpa, Karni S. Moshal, Shailesh R. Agarwal, Robert D. Harvey
Summary: This study revealed that cAMP produced by stimulation of beta(2)-adrenoceptors was unable to reach the SERCA2 pump location, and this compartmentalized response is partly due to PDE2 and PDE3 activity.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Rui Xu, Shi Feng, Zhou Ao, Yingxiang Chen, Congping Su, Xiuling Feng, Qin Fu, Xiaoyan Yang
Summary: Psoriasis is a chronic inflammatory disease that affects a significant portion of the population worldwide. Salmeterol, a long-acting beta(2)-AR agonist, alleviates the severity of psoriasis by inhibiting the proliferation and promoting apoptosis of keratinocytes.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Hao Chen, Ning Cao, Li Wang, Ye Wu, Haojie Wei, Yuming Li, Youyi Zhang, Suli Zhang, Huirong Liu
Summary: This study revealed that beta(1)-AA continuously activates beta(1)-AR by inhibiting receptor endocytosis. Biased activation of the beta(2)-AR/Gi/GRK2 signaling pathway can promote beta(1)-AR endocytosis restricted by beta(1)-AA, terminate signal transduction, and alleviate heart damage.
CELL DEATH DISCOVERY
(2021)
Article
Cardiac & Cardiovascular Systems
Ama Dedo Okyere, Jianliang Song, Viren Patwa, Rhonda L. Carter, Nitya Enjamuri, Anna Maria Lucchese, Jessica Ibetti, Claudio de Lucia, Sarah M. Schumacher, Walter J. Koch, Joseph Y. Cheung, Jeffrey L. Benovic, Douglas G. Tilley
Summary: This study found that the regulation of β2AR through ICL1-9 can enhance the contractility of cardiomyocytes, and promotes RhoA signaling through a G protein-dependent pathway, providing a new approach for the treatment of heart failure.
CARDIOVASCULAR DRUGS AND THERAPY
(2023)
Article
Biology
Hanako Hagio, Wataru Koyama, Shiori Hosaka, Aysenur Deniz Song, Janchiv Narantsatsral, Koji Matsuda, Tomohiro Sugihara, Takashi Shimizu, Mitsumasa Koyanagi, Akihisa Terakita, Masahiko Hibi, Suresh Jesuthasan
Summary: We examined the functionality of animal G-protein-coupled bistable rhodopsins in zebrafish by controlling them into active and inactive states using light application. The Gq-coupled spider Rh1 expressed in hindbrain reticulospinal V2a neurons increased intracellular Ca2+ levels and induced swimming behavior upon light stimulation. The Gi/o-coupled mosquito Opn3, pufferfish TMT opsin, or lamprey parapinopsin expressed in cardiomyocytes caused cardiac arrest, which could be suppressed by pertussis toxin or barium treatment, indicating the regulation of cardiac function by Gi/o-dependent inward-rectifier K+ channels. These rhodopsins are valuable tools for optogenetic control of GPCR-mediated signaling in zebrafish neurons and cardiomyocytes.
Article
Neurosciences
Kevin M. Manz, Jose C. Zepeda, Zack Zurawski, Heidi E. Hamm, Brad A. Grueter
Summary: The nucleus accumbens (NAc) plays a role in behaviors such as addiction and depression. G(i/o)-coupled G-protein-coupled receptors (GPCRs) at glutamatergic synapses onto medium spiny projection neurons (MSNs) regulate these behaviors. In this study, the authors investigated which G(i/o) systems in the NAc utilize G beta gamma-SNARE signaling to inhibit glutamatergic transmission. They found that SNAP25 contributes significantly to the actions of certain GPCRs in dampening glutamatergic transmission.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Hao Chen, Suli Zhang, Ruiqi Hou, Huirong Liu
Summary: This review summarizes the discovery of the beta(1)-AR-Gi pathway and its significance in the treatment of heart diseases.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2022)
Article
Medicine, Research & Experimental
Cancan Lyu, Yuanchao Ye, Maddison M. Lensing, Kay-Uwe Wagner, Ronald J. Weigel, Songhai Chen
Summary: In HER2(+) breast cancer, overactivation of HER2 leads to aberrant G(i/o)-GPCR signaling, promoting cancer progression and resistance to HER2-targeted therapy. Pharmacologically deactivating GPCR signaling can block tumor growth and enhance therapeutic efficacy.
Article
Biochemical Research Methods
Aenne-Dorothea Liebing, Petra Krumbholz, Claudia Staeubert
Summary: This protocol outlines the steps for cloning HA- and FLAG-tagged GPCRs, transiently transfecting CHO-K1 or HEK293-T cells, and measuring intracellular cAMP levels. Additionally, it provides detailed procedures for determining GPCR plasma membrane and total expression levels using enzyme-linked immunosorbent assays.
Article
Cardiac & Cardiovascular Systems
Shelby A. Dahlen, Tyler F. Bernadyn, Alethia J. Dixon, Bo Sun, Jingsheng Xia, Elizabeth A. Owens, Patrick Osei-Owusu
Summary: In this study, the researchers found that the absence of RGS2 and 5 leads to abnormal cardiac structure and function, particularly in male mice. RGS2 and 5 maintain cardiovascular homeostasis by regulating G protein signaling and facilitating cardiomyocyte calcium handling.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Article
Oncology
Cancan Lyu, Yuanchao Ye, Ronald J. Weigel, Songhai Chen
Summary: This study reveals that targeting Gi/o-GPCR signaling is a promising strategy for eradicating cancer stem cells (CSCs) and enhancing HER2-targeted therapy in breast cancer.
Article
Chemistry, Medicinal
Xinxin Li, Runlu Shi, Lingchen Yan, Weiwei Chu, Ruishuang Sun, Binkai Zheng, Shuai Wang, Hui Tan, Xusheng Wang, Ying Gao
Summary: In this study, rhynchophylline was discovered as a promising compound for preventing stress-induced hair graying by inhibiting the NA-β2AR signaling. Through advanced computer-aided drug design techniques, rhynchophylline exhibited strong and stable binding within the active site of beta 2 adrenergic receptors, resulting in a significant reduction of hair graying in a stress-induced mouse model.
NATURAL PRODUCTS AND BIOPROSPECTING
(2023)