Metabolism of nicotine in rat lung microvascular endothelial cells

The Journal of Pharmacy and Pharmacology
Yoshinori OchiaiYorihisa Tanaka

Abstract

The aim of this study was to examine whether cultured rat lung microvascular endothelial cells (LMECs), which constitute the gas-blood barrier, have the ability to metabolize nicotine. Nicotine was biotransformed to cotinine and nicotine N'-oxide by cytochrome 450 (CYP) and flavin-containing monooxyganase (FMO), respectively, in rat LMECs. The intrinsic clearance (Vmax1/Km1) for the cotinine formation was about 20 times as high as that for the trans-nicotine N'-oxide formation in the low-Km phase, indicating that oxidation by CYP was much higher than that by FMO. On the other hand, as shown in Eadie-Hofstee plots, the formation of cis-nicotine N'-oxide was monophasic, whereas the plot for the trans-nicotine N'-oxide formation was clearly biphasic. These results suggest that nicotine N'-oxide was stereoselectively metabolized to cis and trans forms. However, in the high-Km phase there was no significant difference in N'-oxidation between the cis and trans forms. Moreover, we suggest that CYP2C11 and CYP3A2 are key players in the metabolism to cotinine of nicotine in rat LMECs using the respective enzyme inhibitors (tranylcypromine and troleandomycine). On the other hand, methimazole (5 microM) caused 73 and 45% decreases in the ...Continue Reading

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Citations

Mar 22, 2014·In Vitro Cellular & Developmental Biology. Animal·Yukari UedaEiichi Sakurai
Nov 18, 2014·International Journal of Molecular Sciences·Christopher RacineGary O Rankin
Mar 12, 2011·American Journal of Orthodontics and Dentofacial Orthopedics : Official Publication of the American Association of Orthodontists, Its Constituent Societies, and the American Board of Orthodontics·Ahmad SodagarMohammad Javad Kharrazifard
Mar 5, 2010·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Li MaLim Kwong Cheung
Jun 1, 2017·International Journal of Molecular Sciences·Gary O RankinMonica A Valentovic
Jul 2, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Evelyn L CraigRachel F Tyndale
Jan 7, 2020·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Eiichi Sakurai
Nov 21, 2020·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Felix Atawal AndongArinze Ikechukwu Onwurah

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