Leclerc Séverine, Heydel Jean-Marie, Amossé Valérie, Gradinaru Daniela, Cattarelli Martine, Artur Yves, Goudonnet Hervé, Magdalou Jacques, Netter Patrick, Pelczar Hélène, Minn Alain
UMR 7561 CNRS-Université Henri Poincaré-Nancy 1, Faculté de Médecine, BP 184, 54505 Vandoeuvre-lès-Nancy Cedex, France.
Brain Res Mol Brain Res. 2002 Nov 15;107(2):201-13. doi: 10.1016/s0169-328x(02)00455-2.
The aim of the present study was to examine the glucuronidation of a series of odorant molecules by homogenates prepared either with rat olfactory mucosa, olfactory bulb or brain. Most of the odorant molecules tested were efficiently conjugated by olfactory mucosa, whereas olfactory bulb and brain homogenates displayed lower activities and glucuronidated only a few molecules. Important age-related changes in glucuronidation efficiency were observed in olfactory mucosa and bulb. Therefore, we studied changes in expression of two UDP-glucuronosyltransferase isoforms, UGT1A6 and UGT2A1, in 1-day, 1- and 2-week-, 3-, 12- and 24-month-old rats. UGT1A6 was expressed at the same transcriptional level in the olfactory mucosa, bulb and brain, throughout the life period studied. UGT2A1 mRNA was expressed in both olfactory mucosa and olfactory bulb, in accordance with previous results [Mol. Brain Res. 90 (2001) 83], but UGT2A1 transcriptional level was 400-4000 times higher than that of UGT1A6. Moreover, age-dependent variations in UGT2A1 mRNA expression were observed. As it has been suggested that drug metabolizing enzymes could participate in olfactory function, mitral cell electrical activity was recorded during exposure to different odorant molecules in young, adult and old animals. Age-related changes in the amplitude of response after stimulation with several odorant molecules were observed, and the highest responses were obtained with molecules that were not efficiently glucuronidated by olfactory mucosa. In conclusion, the present work presents new evidence of the involvement of UGT activity in some steps of the olfactory process.
本研究的目的是检测一系列气味分子在由大鼠嗅黏膜、嗅球或脑制备的匀浆中的葡糖醛酸化情况。大多数测试的气味分子能被嗅黏膜有效地结合，而嗅球和脑匀浆的活性较低，仅能使少数分子发生葡糖醛酸化。在嗅黏膜和嗅球中观察到了与年龄相关的葡糖醛酸化效率的重要变化。因此，我们研究了1日龄、1周龄、2周龄、3月龄、12月龄和24月龄大鼠中两种尿苷二磷酸葡糖醛酸基转移酶同工型UGT1A6和UGT2A1的表达变化。在整个研究的生命阶段，UGT1A6在嗅黏膜、嗅球和脑中以相同的转录水平表达。UGT2A1 mRNA在嗅黏膜和嗅球中均有表达，与先前的结果一致[《分子脑研究》90(2001)83]，但UGT2A1的转录水平比UGT1A6高400 - 4000倍。此外，观察到UGT2A1 mRNA表达存在年龄依赖性变化。由于有人提出药物代谢酶可能参与嗅觉功能，因此在年轻、成年和老年动物暴露于不同气味分子期间记录了二尖瓣细胞的电活动。观察到在用几种气味分子刺激后反应幅度的年龄相关变化，并且对于那些不能被嗅黏膜有效葡糖醛酸化的分子获得了最高反应。总之，本研究提供了UGT活性参与嗅觉过程某些步骤的新证据。
