ArticleThe Journal of biological chemistry2011
Orientation and cellular distribution of membrane-bound catechol-O-methyltransferase in cortical neurons: implications for drug development.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 3 syntheses or guidelines pooled it, 75 citations in OpenAlex.
- Connecting DCX, COMT and FMR1 in social behavior and cognitive impairment.Behavioral and brain functions : BBF · 2022Pooled it
- Association Between Polymorphisms of DRD2, COMT, DBH, and MAO-A Genes and Migraine Susceptibility: A Meta-Analysis.Medicine · 2015Pooled it
- Role of COMT in ADHD: a systematic meta-analysis.Molecular neurobiology · 2014Pooled it
- COMT Val(158)Met genotype determines the direction of cognitive effects produced by catechol-O-methyltransferase inhibition.Biological psychiatry · 2012Trial
- Catechol-Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Ontogeny of Catechol-O-Methyltransferase Expression in the Rat Prefrontal Cortex: Effects of Methamphetamine Exposure.Developmental neuroscience · 2026Article
- Decoding the impact of the placebo response in clinical trials for chronic cough.ERJ open research · 2024Article
- Sex dimorphism controls dysbindin-related cognitive dysfunctions in mice and humans with the contribution of COMT.Molecular psychiatry · 2024Article
- The dopamine hypothesis for ADHD: An evaluation of evidence accumulated from human studies and animal models.Frontiers in psychiatry · 2024Review
- A growing understanding of the role of muscarinic receptors in the molecular pathology and treatment of schizophrenia.Frontiers in cellular neuroscience · 2023Review
- Neurochemical, histological, and behavioral profiling of the acute, sub-acute, and chronic MPTP mouse model of Parkinson's disease.Journal of neurochemistry · 2023Article
- Diabetes and Cognitive Impairment: A Role for Glucotoxicity and Dopaminergic Dysfunction.International journal of molecular sciences · 2021Review
- Motivational learning biases are differentially modulated by genetic determinants of striatal and prefrontal dopamine function.Journal of neural transmission (Vienna, Austria : 1996) · 2021Article
- The genotoxicity potential of luteolin is enhanced by CYP1A1 and CYP1A2 in human lymphoblastoid TK6 cells.Toxicology letters · 2021Article
- Estrogens in schizophrenia: progress, current challenges and opportunities.Current opinion in psychiatry · 2021Review
- In silico discovery and evaluation of phytochemicals binding mechanism against human catechol-O-methyltransferase as a putative bioenhancer of L-DOPA therapy in Parkinson disease.Genomics & informatics · 2021Article
- Analytical methodologies for sensing catechol-Journal of pharmaceutical analysis · 2021Review
- Effort-related decision making in humanized COMT mice: Effects of ValPharmacology, biochemistry, and behavior · 2020Article
- RasGRP1 is a causal factor in the development of l-DOPA-induced dyskinesia in Parkinson's disease.Science advances · 2020Article
- Quantitative Proteomics Reveals Cellular Off-Targets of a DDR1 Inhibitor.ACS medicinal chemistry letters · 2020Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Catechol-O-methyltransferase (COMT) is a key enzyme for inactivation and metabolism of catechols, including dopamine, norepinephrine, caffeine, and estrogens. It plays an important role in cognition, arousal, pain sensitivity, and stress reactivity in humans and in animal models. The human COMT gene is associated with a diverse spectrum of human behaviors and diseases from cognition and psychiatric disorders to chronic pain and cancer. There are two major forms of COMT proteins, membrane-bound (MB) COMT and soluble (S) COMT. MB-COMT is the main form in the brain. The cellular distribution of MB-COMT in cortical neurons remains unclear and the orientation of MB-COMT on the cellular membrane is controversial. In this study, we demonstrate that MB-COMT is located in the cell body and in axons and dendrites of rat cortical neurons. Analyses of MB-COMT orientation with computer simulation, flow cytometry and a cell surface enzyme assay reveal that the C-terminal catalytic domain of MB-COMT is in the extracellular space, which suggests that MB-COMT can inactivate synaptic and extrasynaptic dopamine on the surface of presynaptic and postsynaptic neurons. Finally, we show that the COMT inhibitor tolcapone induces cell death via the mechanism of apoptosis, and its cytotoxicity is dependent on dosage and correlated with COMT Val/Met genotypes in human lymphoblastoid cells. These results suggest that MB-COMT specific inhibitors can be developed and that tolcapone may be less hazardous at low doses and in specific genetic backgrounds.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.