Treatment of primary cultured cortical cells with erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA), an inhibitor of adenosine deaminase (ADAR), for 6 d significantly and concentration-dependently reduced the editing efficacy at sites C and D but not at site A or B of 5-HT2CR mRNA. The treatment failed to affect the editing of ADAR-2 pre-mRNA and a subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptor (GluR2) mRNA. These findings suggest that EHNA is useful for clarifying the functional roles of 5-HT2CR mRNA editing at sites C and D.
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http://dx.doi.org/10.1248/bpb.33.527 | DOI Listing |
Front Pharmacol
December 2022
Center for Addiction Research, University of Texas Medical Branch, Galveston, TX, United States.
Drug overdose deaths involving cocaine have skyrocketed, an outcome attributable in part to the lack of FDA-approved medications for the treatment of cocaine use disorder (CUD), highlighting the need to identify new pharmacotherapeutic targets. Vulnerability to cocaine-associated environmental contexts and stimuli serves as a risk factor for relapse in CUD recovery, with individual differences evident in the motivational aspects of these cues. The medial prefrontal cortex (mPFC) provides top-down control of striatal circuitry to regulate the incentive-motivational properties of cocaine-associated stimuli.
View Article and Find Full Text PDFDrug Discov Ther
December 2021
Global Center for Natural Resources Sciences, Graduate Schools of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
An electrophysiological bioassay was used to isolate the active compound from Hochuekkito (HET), which the current authors previously described as having potent agonist action against serotonin 2C receptors (5-HT2CR). Synthetic 5-HT2CR mRNA was injected into Xenopus oocytes to specifically express these receptors. Crude extracts and purified products were subjected to an electrophysiological bioassay using the voltage clamp method.
View Article and Find Full Text PDFFront Neurosci
January 2020
Department of Basic Geriatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Hum Mol Genet
September 2019
Psychology, Cardiff University, Cardiff, UK.
Prader-Willi syndrome (PWS) is a neurodevelopmental disorder caused by deletion or inactivation of paternally expressed imprinted genes on human chromosome 15q11-q13. In addition to endocrine and developmental issues, PWS presents with behavioural problems including stereotyped behaviour, impulsiveness and cognitive deficits. The PWS genetic interval contains several brain-expressed small nucleolar (sno) RNA species that are subject to genomic imprinting, including snord115 that negatively regulates post-transcriptional modification of the serotonin 2C receptor (5-HT2CR) pre-mRNA potentially leading to a reduction in 5-HT2CR function.
View Article and Find Full Text PDFSci Rep
March 2019
Medical Faculty, Core Facility Transgenic animal and genetic engineering Models (TRAM), University of Muenster, Von-Esmarch-Str. 56, D-48149, Muenster, Germany.
Serotonin 5-HT2C receptor is a G-protein coupled excitatory receptor that regulates several biochemical pathways and has been implicated in obesity, mental state, sleep cycles, autism, neuropsychiatric disorders and neurodegenerative diseases. The activity of 5-HT2CR is regulated via alternative splicing and A to I editing of exon Vb of its pre-mRNA. Snord115 is a small nucleolar RNA that is expressed in mouse neurons and displays an 18-nucleotide base complementary to exon Vb of 5-HT2CR pre-mRNA.
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