At the periphery of the olfactory system, the binding of odorants on olfactory receptors (ORs) is usually thought to be the first level of the perception of smell. However, at this stage, there is evidence that other molecular mechanisms also interfere with this chemoreception by ORs. These perireceptor events are mainly supported by two groups of proteins present in the olfactory nasal mucus or in the nasal epithelium. Odorantbinding proteins (OBPs), the first group of proteins have been investigated for many years. OBPs are small carrier proteins capable of binding odorants with affinities in the micromolar range. Although there is no absolute evidence to support their functional roles in vertebrates, OBPs are good candidates for the transport of inhaled odorants towards the ORs via the nasal mucus. The second group of proteins involves xenobiotic metabolizing enzymes, which are strongly expressed in the olfactory epithelium and supposed to be involved in odorant transformation, degradation, and/or olfactory signal termination. Following an overview of these proteins, this review explores their roles, which are still a matter of debate. Anat Rec, 296:1333Rec, 296: -1345

This article is available online at http://dmd.aspetjournals.org ABSTRACT:The pregnane X receptor (PXR) has three known major transcript variants resulting from alternative splicing. The less well characterized variants T2 and T3 are identical to the well described variant T1 except for a 39-amino acid N-terminal extension in T2 and an internal 37-amino acid deletion in T3. We have developed reverse transcription-polymerase chain reaction (RT-PCR) methods to detect and quantify each human PXR (hPXR) in human liver and intestinal tissues and HepG2 and Caco-2 cell lines. All three isoforms were expressed in hepatic cells, whereas only T1 transcripts were found in Caco-2 cells. In general, most normal human liver and intestinal mucosa contained all three hPXR variants, but considerable interindividual variation in expression levels was found. The effect of each hPXR variant on expression of UDPglucuronosyltransferase (UGT) UGT1A and UGT2B family isoforms was investigated in transiently transfected HepG2 and Caco-2 cells. As a family, UGT1A transcripts were up-regulated by T1 and T2 but not T3. Isoform-specific RT-PCR revealed that UGT1A1, 1A3, and 1A4 were the major isoforms induced in both cell lines. The levels of several UGT1A isoforms were also examined in human liver samples from a number of donors with characterized PXR expression. The data suggest that individual variation in PXR expression may account for differential expression of some UGT isoforms between subjects.

ABSTRACT:trans-Resveratrol is a polyphenol present in several plant species. Its chemopreventive properties against several diseases have been largely documented. To validate a model for the study of the factors influencing its biological fate at the hepatic level, the metabolism and the efflux of resveratrol were studied in the human hepatoblastoma cell line, HepG2. Comparative high-performance liquid chromatography analysis of cell culture media before and after deconjugation showed that resveratrol was rapidly conjugated; at the concentration of 10 M, it was entirely metabolized at 8 h of incubation. Two main resveratrol metabolites, monosulfate and disulfate, were identified by atmospheric pressure chemical