| Title | D2-receptor mediated alterations in the metabolic efficacy of the liver and other extrahepatic tissues | |
| Authors | Panagiotis Harkitis¹, Alarick Lang Matti², Marios Marselos¹, Andreas Fotopoulos³, Albucharali Gihad³ and Maria Konstandi¹
1. Department of Pharmacology and 3. Department of Nuclear Medicine, Medical School, University of Ioannina, Ioannina GR-451 10, Greece 2. Division of Biochemistry, Faculty of Uppsala, Box 578S75123, Uppsala, Sweden |
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| Citation | Harkitis, P., Lang Matti, A., Marselos, M., Fotopoulos, A., Gihad. A. et al: D2-receptor mediated alterations in the metabolic efficacy of the liver and other extrahepatic tissues, Epitheorese Klin. Farmakol. Farmakokinet. 20(2): 171-173 (2006) | |
| Publication Date | Accepted for publication: 19-20 May 2006 | |
| Full Text Language | English | |
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| Keywords | CYP1A, CYP2B, CYP2E1, 02-receptors, rat. | |
| Other Terms | review article | |
| Summary | Various cytochromes and in particular those that belong to the CYP1A, CYP2B and CYP2E subfamilies, are involved in the metabolism of a broad variety of drugs, environmental pollutants and carcinogens among others. The concomitant administration of drugs and xenobiotics that modify the expression of the aforementioned CYP genes, may lead to complications in drug therapy and trigger severe side effects. In this study, the involvement of D2-receptor linked pathways in the regulation of cytochromes CYP1A1, CYP1A2, CYP2B1/2 and CYP2E1 was investigated in the liver, kidney and lung of rats. The data of this study showed that L-DOPA markedly increased 7-methoxyresorufin O-demethylase (MROD) and 7-ethoxyresorufin deethylase (EROD) activities (dependent on CYP1A isozymes) in the lungs, whereas L-DOPA did not affect these activities in the liver and kidney. In contrast, 7- pentoxyresorufin O-dealkylase (PROD) activity (dependent on CYP2B isozymes) was markedly increased by L-DOPA in all tissues tested. Blockade of D2-dopaminergic receptors with sulpiride suppressed hepatic EROD, while in- creased it in the lungs. PROD and p-nitrophenol hydroxylase (PNP) activity (dependent on CYP2E) were sup- pressed by sulpiride only in the liver. PROD was increased by the drug in the kidney, while no change was observed in the lung. On the other hand, bromocryptine-induced stimulation of D2-receptors increased MROD only in the lung and EROD only in the liver. PROD and PNP activities were not affected by bromocryptine. Similar alterations were found at protein level. These data show that drugs that affect central and/or peripheral dopaminergic signaling pathways may modify in a tissue-specific and enzyme- specific manner the expression of CYP isozymes, which are involved in the metabolism of drugs, toxicants and carcinogens. This in turn may lead to severe complications in drug therapy and affect the health and disease. | |
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Online ISSN 1011-6575
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