Article
Pharmacology & Pharmacy
Andrea N. Beltran Gonzalez, Manuel I. Lopez Pazos, Mariana del Vas, Daniel J. Calvo
Summary: Histamine can function as a neurotransmitter and neuromodulator in addition to its role as a mediator of the immune response. It was previously shown to act as a positive modulator on various GABAA receptor subtypes, but its effects on GABA(A)rho 1 receptors had not been studied. This research demonstrated that histamine inhibits GABAA.1 receptor-mediated responses through competitive antagonism on GABA(A rho)1 receptors.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Gastroenterology & Hepatology
Zhongcheng Shi, Yuko Mori-Akiyama, Wa Du, Robert Fultz, Yanling Zhao, Wenly Ruan, Susan Venable, Melinda A. Engevik, James Versalovic
Summary: This study found that blocking H2R signaling enhances the proinflammatory responses of mature neutrophils and suppresses neutrophil maturation, leading to accelerated progression of inflammation-associated colonic tumorigenesis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Agronomy
Toshifumi Nakao, Shinichi Banba
Summary: The research demonstrates the differential antagonist activities of meta-diamides on insect and human receptors by studying the effects of equivalent mutations in human GABA receptors. This study reveals the underlying mechanisms of selectivity of meta-diamides between insect RDL and human GABA and glycine receptors.
PEST MANAGEMENT SCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Chigusa Shimizu-Okabe, Shiori Kobayashi, Jeongtae Kim, Yoshinori Kosaka, Masanobu Sunagawa, Akihito Okabe, Chitoshi Takayama
Summary: This study describes the transmission of GABAergic and glycinergic neurotransmitters and inhibitory networks in the mature mouse spinal cord. The research also provides insights into the developmental formation of these networks, including neuronal differentiation, synapse formation, maturation of removal systems, and changes in their function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Elena I. Solntseva, Julia V. Bukanova, Rodion Kondratenko, Eva Kudova
Summary: The negative impact of corticosteroids on mental illness is still unclear. This study found that corticosterone and other corticosteroids could accelerate the desensitization of glycine receptors, while some corticosteroids could also accelerate the desensitization of GABA-A receptors. The results suggest that increased desensitization of these receptors by corticosteroids may contribute to brain dysfunction under chronic stress and identify potential selective modulators of these receptors.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Neurosciences
Diana Lucaci, Xiao Yu, Paul Chadderton, William Wisden, Stephen G. Brickley
Summary: We investigated the effects of histamine and GABA release from TMN axons projecting to the PFC on circuit processing. Histamine stimulated fast-spiking interneurons, while released GABA enhanced tonic inhibition on PyrNs. Histamine-induced gain changes were blocked by histamine receptor antagonists, while GABA-induced gain changes were blocked by GABAA receptor antagonists. The GABA modulation of PyrN excitability by TMNHDC axons increased significantly in older mice, potentially enhancing information processing and maintaining cognition in aging individuals.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Agronomy
Toshifumi Nakao, Shinichi Banba
Summary: This study identifies important amino acids critical for the function of the Drosophila Rdl GABA receptor through mutational studies and receptor modeling. The interactions between TM3 and TM4, as well as intersubunit interactions, are crucial for channel gating, while intrasubunit interactions between TM2 and TM3 domains are less significant for the Drosophila Rdl GABA receptor.
PEST MANAGEMENT SCIENCE
(2021)
Article
Neurosciences
Kiki J. Chen, Ryan Yoshimura, Clarissa Adriana Edmundo, Tri Minh Truong, Olivier Civelli, Amal Alachkar, Geoffrey W. Abbott
Summary: By investigating the GABA binding site that activates KCNQ3, it was found that this direct interaction has significant effects on mouse behavior, especially in regulating nociception and stress responses. This finding provides new targets for treating neurological and psychiatric disorders.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Biology
Morgan McDonald, Natalie Paige Griffin, Emma Howell, Dingchen Li, Sophia Harnew-Spradley, Patrick Rodriguez, Abigail Lancaster, Feza Umutoni, Jordan Besh, Chris Shelley
Summary: Sea urchins are genetically closer to vertebrates but lack a brain. Little is known about the neurobiology of adult sea urchins. In this study, the effects of neurotransmitter receptor antagonists on the righting response of sea urchins were investigated. The results showed that glycine and adrenergic receptors are involved in tube foot movement, while dopamine receptors are involved in the neural processing of righting behavior.
JOURNAL OF EXPERIMENTAL BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Ibrahim Alrashdi, Amal Alsubaiyel, Michele Chan, Emma E. Battell, Abdel Ennaceur, Miles A. Nunn, Wayne Weston-Davies, Paul L. Chazot, Ilona Obara
Summary: This study reveals the potential of Votucalis in inhibiting histaminergic itch and neuropathic pain. Peripheral administration of Votucalis shows longer duration and better anti-itch effect, while mechanical hypersensitivity is more efficiently suppressed compared to thermal hypersensitivity. These findings highlight the importance of histamine in regulating itch and chronic neuropathic pain, and propose a therapeutic potential for Votucalis in scavenging peripherally released histamine.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Ana -Maria Oprisoreanu, Fari Ryan, Claire Richmond, Yuliya Dzekhtsiarova, Neil O. Carragher, Thomas Becker, Samuel David, Catherina G. Becker
Summary: Prolonged inflammation after spinal cord injury is detrimental to recovery. We designed a rapid drug screening paradigm in larval zebrafish and tested hit compounds in a mouse spinal cord injury model to find pharmacological modulators of inflammation response. Our screen revealed H2 receptor signaling as a promising target for future therapeutic interventions in spinal cord injury.
Article
Neurosciences
Hajime Hirasawa, Naofumi Miwa, Shu-Ichi Watanabe
Summary: The study investigated the contribution of inhibitory circuits to ON- and OFF-responses (b- and d-waves) in the full-field ERG of newt retina. Results indicated that different synaptic transmission blockers affected the amplitudes of the b- and d-waves, revealing a circuitry mechanism for the regulation of the d-wave and offering insight into the underlying mechanisms of ERG formation.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Martin Norgaard, Vincent Beliveau, Melanie Ganz, Claus Svarer, Lars H. Pinborg, Sune H. Keller, Peter S. Jensen, Douglas N. Greve, Gitte M. Knudsen
Summary: The study presents a high-resolution atlas of BZR densities in the human brain based on in vivo PET data, revealing the association between BZR protein density and mRNA expression for individual subunits in the GABA A R.
Article
Multidisciplinary Sciences
Liying Zhang, Charlotte Simonsen, Lucie Zimova, Kaituo Wang, Lavanya Moparthi, Rachelle Gaudet, Maria Ekoff, Gunnar Nilsson, Ute A. Hellmich, Viktorie Vlachova, Pontus Gourdon, Peter M. Zygmunt
Summary: This study uses cryo-EM and electrophysiology to identify a cannabinoid binding site in TRPV2 that is distinct from cannabidiol, which could potentially be a drug target for the treatment of inflammation and immune-mediated diseases.
NATURE COMMUNICATIONS
(2022)
Article
Agriculture, Multidisciplinary
Zhong Qiang Jia, Su Gui Zhang, Ying Wang, Jun Heng Pan, Fei Fan Liu, En Ling Zhan, Eman Atef Fouad, Ya Li Fu, Qi Rui Pan, Chun Qing Zhao
Summary: SlRdl1 and SlRdl2 are essential for GABA-induced neural signal transmission in Spodoptera litura. Knockout of SlRdl1 and SlRdl2 resulted in increased mortality and prolonged larval and pupal duration. Only knockout of SlRdl1 affected flight capability, significantly increasing flight time and distance. The study provides new insights into lepidopteran insect ionotropic γ-aminobutyric acid receptors (iGABARs) research.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)