Article
Biochemistry & Molecular Biology
Spencer T. Kim, Emma J. Doukmak, Michelle Shanguhyia, Dylan J. Gray, Rachel C. Steinhardt
Summary: Orthogonal recreation of the signaling profile of a chemical synapse is a current challenge in neuroscience. In this study, photocaged compounds were used to recreate the rapid rise and fall in activation at a chemical synapse. By conjugating these compounds to a subtype-selective agonist and antagonist, the bioactive drugs could be released upon illumination with specific colors of light. The kinetics of photolysis and the control of intracellular calcium flux were characterized, allowing for greater spatiotemporal control of 5-HT2C modulation.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Neurosciences
Nana Gao, Wei Zheng, Tiliwaerde Murezati, Wei Gu, Xiaorong Li, Zengliang Jin
Summary: The study suggests that GW117 functions as a serotonin 2C (5-HT2C) receptor antagonist and melatonin type 1 and 2 (MT1/MT2) receptor agonist, showing evident antidepressant and anxiolytic effects.
CNS NEUROSCIENCE & THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Esraa Haji, Saeed Al Mahri, Yumna Aloraij, Shuja Shafi Malik, Sameer Mohammad
Summary: ADR beta(3) is a crucial receptor involved in lipid metabolism regulation, with a genetic variant W64R linked to diabetes and obesity, showing no significant functional differences compared to the wild-type counterpart.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Fan Yang, Shenglong Ling, Yingxin Zhou, Yanan Zhang, Pei Lv, Sanling Liu, Wei Fang, Wenjing Sun, Liaoyuan A. Hu, Longhua Zhang, Pan Shi, Changlin Tian
Summary: Using single-particle cryo-electron microscopy, the structures of beta(2)AR-G alpha(s)beta gamma in complex with partial agonist salbutamol or full agonist isoprenaline were determined, revealing differences in binding affinity, hydrogen bonding interactions, hydrophobic interactions, and conformational changes between the two agonists. Stronger interactions between intracellular loop 2 or 3 (ICL2 or ICL3) of beta(2)AR and G alpha(s) observed in the salbutamol complex indicate potential mechanisms for decreased phosphorylation and beta(2)AR desensitization.
NATIONAL SCIENCE REVIEW
(2021)
Article
Biochemistry & Molecular Biology
Rachel A. Matt, Frederick G. Westhorpe, Rosemary F. Romuar, Payal Rana, Joel R. Gever, Anthony P. Ford
Summary: This study pharmacologically analyzed the function of brain adrenoceptors and provided insights for innovative therapeutic interventions to compensate for locus coeruleus decline in neurodegenerative diseases. The results showed broad beta 2-AR functional expression across several human brain cell types, suggesting noradrenergic regulation from the locus coeruleus exerts heterocellular neuroexcitatory and homeostatic influence.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jie Yu, Hongtao Zhu, Remigijus Lape, Timo Greiner, Juan Du, Wei Lu, Lucia Sivilotti, Eric Gouaux
Summary: Using electrophysiology and cryo-EM reconstructions, this study investigated the mechanism of partial agonist action on neurotransmitter receptors, revealing new conformational states along the receptor reaction pathway. The results demonstrated that partial agonists can occupy closed channel states bound by agonists, affecting the receptor channel's open probability.
Article
Medicine, Research & Experimental
Seungkirl Ahn, Harm Maarsingh, Julia K. L. Walker, Samuel Liu, Akhil Hegde, Hyeje C. Sumajit, Alem W. Kahsai, Robert J. Lefkowitz
Summary: This article investigates the potential of β2AR-selective positive allosteric modulators (PAMs) in the treatment of asthma and other obstructive respiratory diseases. The results demonstrate that these PAMs can enhance the binding and downstream signaling of β2-agonists to β2ARs in guinea pigs and humans, thereby promoting bronchodilation and protection.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Pharmacology & Pharmacy
Veronique Pons, Cedric Garcia, Naomi Tidten-Luksch, Aengus Mac Sweeney, Eva Caroff, Celine Gales, Markus A. Riederer
Summary: This study demonstrates the inverse agonistic effect of Selatogrel on the P2Y12 receptor, which is more potent than Ticagrelor. Selatogrel stabilizes the inactive state of the receptor and prevents ADP binding, thereby inhibiting platelet activation.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chi Xu, Yun Cheng, Manman Han, Yimin Tao, Jing-Gen Liu
Summary: Our study found that activation of adenosine A1 receptor inhibits the MAPK signaling pathway mediated by delta opioid receptor through heterologous desensitization of the Raf-1/MEK/ERK cascade.
NEUROCHEMICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Soon-Young Na, Ki-Sun Kim, Yoon Seok Jung, Don-Kyu Kim, Jina Kim, Sung Jin Cho, In-Kyu Lee, Jongkyeong Chung, Jeong-Sun Kim, Hueng-Sik Choi
Summary: In this study, we found that GSK5182 stabilizes the ERR gamma protein by inhibiting its ubiquitination and recruiting a corepressor through the AF-2 domain. These findings suggest that GSK5182 regulates ERR gamma by a unique molecular mechanism, increasing the inactive form of ERR gamma via inhibition of ubiquitination.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Mengwen Shi, Jiaxin Tang, Chengmei Yang, Guanlong Guo, Huaxing Ou, Weihai Chen
Summary: This study found that the reversal effect of 5-HT2A receptor inverse agonists on PPI deficits is achieved through modulation of the nucleus accumbens and ventral hippocampus, rather than the medial prefrontal cortex or ventral tegmental area. These findings contribute to the exploration of the antipsychotic effects of 5-HT2A receptor inverse agonists by identifying the critical brain areas involved in PPI deficits reversal.
Article
Biochemistry & Molecular Biology
Sahar S. Alghamdi, Suni M. Mustafa, Bob M. Moore
Summary: Research focuses on CB2 as a therapeutic target for neuroinflammatory diseases, aiming to shift microglia bias to a pro-wound healing phenotype. Compound 40 demonstrates increased potency and efficacy for cAMP stimulation compared to SMM189, effectively biasing microglia towards a pro-wound healing phenotype.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Genetics & Heredity
Jia-Hui Sun, Jiang Chen, Fernando Eduardo Ayala Valenzuela, Carolyn Brown, Diane Masser-Frye, Marilyn Jones, Leslie Patron Romero, Berardo Rinaldi, Wenhui Laura Li, Qing-Qing Li, Dan Wu, Benedicte Gerard, Erin Thorpe, Allan Bayat, Yun Stone Shi
Summary: A pathogenic missense variant in the GRIA3 gene was identified in a female patient with severe epilepsy and global developmental delay. This variant enhances glutamate signaling by strengthening the activity of glutamate receptors, leading to epileptic encephalopathy and global developmental delay.
Article
Neurosciences
Olena A. Petrushenko, Anastasiiya O. Stratiievska, Mariia O. Petrushenko, Elena A. Lukyanetz
Summary: This study investigated the dynamics of calcium transients in DRG neurons associated with TRPV1 channel desensitization and the effect of P2 receptor activation on this process. It was found that TRPV1 channels are mainly present in small nociceptive neurons, while P2 receptors are present in all types of neurons. ATP application can restore the response to capsaicin in these neurons.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Parthasaradhireddy Tanguturi, Vibha Pathak, Sixue Zhang, Omar Moukha-Chafiq, Corinne E. Augelli-Szafran, John M. Streicher
Summary: The study successfully developed novel inverse agonists and irreversible antagonists for the delta opioid receptor, providing new tools to investigate its biology or potential therapeutics.