ArticleThe Journal of pharmacology and experimental therapeutics2010
Role of CYP2A5 in the clearance of nicotine and cotinine: insights from studies on a Cyp2a5-null mouse model.
Article in The Journal of pharmacology and experimental therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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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.
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Who cites it
51 citing papers in PubMed, 90 citations in OpenAlex.
- Article
- Nicotinic acetylcholine receptors and learning and memory deficits in Neuroinflammatory diseases.Frontiers in neuroscience · 2023Review
- Nicotine alleviates MPTP-induced nigrostriatal damage through modulation of JNK and ERK signaling pathways in the mice model of Parkinson's disease.Frontiers in pharmacology · 2023Article
- Genetic differences in nicotine sensitivity and metabolism in C57BL/6J and NOD/ShiLtJ mouse strains.Neuropharmacology · 2022Article
- Assessing cytochrome P450 function using genetically engineered mouse models.Advances in pharmacology (San Diego, Calif.) · 2022Review
- Early-life nicotine or cotinine exposure produces long-lasting sleep alterations and downregulation of hippocampal corticosteroid receptors in adult mice.Scientific reports · 2021Article
- PPARα agonist WY-14,643 enhances ethanol metabolism in mice: Role of catalase.Free radical biology & medicine · 2021Article
- Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with AberrantInternational journal of molecular sciences · 2020Article
- Prenatal smoke exposure induces persistentEpigenetics · 2020Article
- Chronic electronic cigarette use elicits molecular changes related to pulmonary pathogenesis.Toxicology and applied pharmacology · 2020Article
- Reduced Chronic Toxicity and Carcinogenicity in A/J Mice in Response to Life-Time Exposure to Aerosol From a Heated Tobacco Product Compared With Cigarette Smoke.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- The Impact of Sex on Changes in Plasma Corticosterone and Cotinine Levels Induced by Nicotine in C57BL/6J Mice.Brain sciences · 2020Article
- Induction via Functional Protein Stabilization of Hepatic Cytochromes P450 upon gp78/Autocrine Motility Factor Receptor (AMFR) Ubiquitin E3-Ligase Genetic Ablation in Mice: Therapeutic and Toxicological Relevance.Molecular pharmacology · 2019Article
- A mouse model for chronic intermittent electronic cigarette exposure exhibits nicotine pharmacokinetics resembling human vapers.Journal of neuroscience methods · 2019Article
- Suppressed hepatocyte proliferation via a ROS-HNE-P21 pathway is associated with nicotine- and cotinine-enhanced alcoholic fatty liver in mice.Biochemical and biophysical research communications · 2019Article
- CYP2A6 is associated with obesity: studies in human samples and a high fat diet mouse model.International journal of obesity (2005) · 2019Article
- Dynamic changes in lung responses after single and repeated exposures to cigarette smoke in mice.PloS one · 2019Article
- Nicotine enhances alcoholic fatty liver in mice: Role of CYP2A5.Archives of biochemistry and biophysics · 2018Article
- Cytochrome P450s and Alcoholic Liver Disease.Current pharmaceutical design · 2018Review
- Enduring effects of perinatal nicotine exposure on murine sleep in adulthood.American journal of physiology. Regulatory, integrative and comparative physiology · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
CYP2A5, a mouse cytochrome P450 monooxygenase that shows high similarities to human CYP2A6 and CYP2A13 in protein sequence and substrate specificity, is expressed in multiple tissues, including the liver, kidney, lung, and nasal mucosa. Heterologously expressed CYP2A5 is active in the metabolism of both endogenous substrates, such as testosterone, and xenobiotic compounds, such as nicotine and cotinine. To determine the biological and pharmacological functions of CYP2A5 in vivo, we have generated a Cyp2a5-null mouse. Homozygous Cyp2a5-null mice are viable and fertile; they show no evidence of embryonic lethality or developmental deficits; and they have normal circulating levels of testosterone and progesterone. The Cyp2a5-null mouse and wild-type mouse were then used for determination of the roles of CYP2A5 in the metabolism of nicotine and its major circulating metabolite, cotinine. The results indicated that the Cyp2a5-null mouse has lower hepatic nicotine 5'-hydroxylation activity in vitro, and slower systemic clearance of both nicotine and cotinine in vivo. For both compounds, a substantially longer plasma half-life and a greater area under the concentration-time curve were observed for the Cyp2a5-null mice, compared with wild-type mice. Further pharmacokinetics analysis confirmed that the brain levels of nicotine and cotinine are also influenced by the Cyp2a5 deletion. These findings provide direct evidence that CYP2A5 is the major nicotine and cotinine oxidase in mouse liver. The Cyp2a5-null mouse will be valuable for in vivo studies on the role of CYP2A5 in drug metabolism and chemical toxicity, and for future production of CYP2A6- and CYP2A13-humanized mouse models.
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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.