Glucuronidation of odorant molecules in the rat olfactory system: activity, expression and age-linked modifications of UDP-glucuronosyltransferase isoforms, UGT1A6 and UGT2A1, and relation to mitral cell activity.
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.
Leclerc
Séverine
S
UMR 7561 CNRS-Université Henri Poincaré-Nancy 1, Faculté de Médecine, BP 184, 54505 Vandoeuvre-lès-Nancy Cedex, France.
Heydel
Jean-Marie
JM
Amossé
Valérie
V
Gradinaru
Daniela
D
Cattarelli
Martine
M
Artur
Yves
Y
Goudonnet
Hervé
H
Magdalou
Jacques
J
Netter
Patrick
P
Pelczar
Hélène
H
Minn
Alain
A
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D014453:Glucuronosyltransferase / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009004:Monosaccharide Transport Proteins; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009812:Odorants; D009830:Olfactory Bulb / Q000187:drug effects / Q000201:enzymology; D009833:Olfactory Pathways / Q000187:drug effects / Q000201:enzymology*; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000201:enzymology; D020033:Protein Isoforms / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018035:Receptors, Odorant / Q000187:drug effects / Q000378:metabolism*; D012903:Smell / Q000187:drug effects / Q000502:physiology*; D013687:Telencephalon / Q000187:drug effects / Q000201:enzymology*; D014535:Uridine Diphosphate Glucuronic Acid / Q000378:metabolism*; D000099237:UDP-Galactose Translocators
D014453:Glucuronosyltransferase; D009004:Monosaccharide Transport Proteins; D020033:Protein Isoforms; D018035:Receptors, Odorant; D014535:Uridine Diphosphate Glucuronic Acid; D000099237:UDP-Galactose Translocators