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Remarkable substrate-inhibitor properties of nicotine enantiomers towards a guinea pig lung aromatic azaheterocycle N-methyltransferase
Authors:K C Cundy  P A Crooks  C S Godin
Institution:1. Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China;2. Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, Shanghai 200433, China;3. Department of Pharmacy, The 98th Hospital of PLA, HuZhou 313000, China;1. Biology Department, College of Science, Sultan Qaboos University, P.O. Box 36, Muscat 123, Oman;2. Biochemistry Department, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box 35, Muscat, Oman;3. Electron Microscopy Unit, Pathology Department, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box 35, Muscat 123, Oman;1. Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP), Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900 São Paulo, Brazil;2. Ophidiarium LNN-FMRP-USP/INeC, Ribeirão Preto Medical School of the University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900 São Paulo, Brazil;3. Behavioural Neurosciences Institute (INeC), Avenida do Café, 2450, Ribeirão Preto, 14050-220 São Paulo, Brazil;4. Dracena Medical School (UNIFADRA-FUNDEC), Rua Bahia, 332, Dracena, 17900-000 São Paulo, Brazil;5. Arthritis Research UK Pain Centre and School of Life Sciences, QMC, University of Nottingham, Nottingham NG7 2UH, United Kingdom;6. School of Physiology, Pharmacology & Neuroscience, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, United Kingdom;7. Pacific Biosciences Research Centre, University of Hawaii at Manoa, Honolulu, HI 96822, USA;8. University of São Paulo Neurobiology of Emotions Research Centre (NAP-USP-NuPNE), Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP), Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900 São Paulo, Brazil;1. School of Engineering and Technology, Central Michigan University, 1200 South Franklin Street, Mt Pleasant, MI 48858, USA;2. Department of Mechanical Engineering, California Baptist University, Riverside, CA 92504, USA;3. Systems Toxicology & Exposure Science, Pacific Northwest National Laboratory, Richland, WA 99352, USA;4. Aerosol Respiratory Dosimetry Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest SE, Albuquerque, NM 87108, USA;1. CINTESIS.UA, Department of Education and Psychology, University of Aveiro, Portugal;2. William James Center for Research, ISPA-Instituto Universitário, Lisbon, Portugal;3. Department of Clinical Neuroscience, Division for Psychology, Karolinska Institutet, Sweden;4. Faculty of Psychology, Universidad Autónoma de Madrid, Spain;5. Department of Psychology and Education, The University of Beira Interior, Portugal;6. Institute of Health Sciences, Portuguese Catholic University, Portugal
Abstract:The kinetics of nicotine methylation by guinea pig lung homogenates has been investigated. An interesting stereospecificity has been observed for nicotine enantiomers. R-(+)-Nicotine is a substrate Km = 1.42 X 10(-5)M for an SAM-dependent guinea pig lung aromatic azaheterocycle N-methyltransferase, whereas S-(-)-nicotine acts as a competitive inhibitor (Ki = 6.25 X 10(-5)M) of the N-methylation of its antipode.
Keywords:
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