title: Cytochromes P450 NMa, NMb (2G1), and LM4 (1A2) are differentially expressed during development in rabbit olfactory mucosa and liver.
abstract: Mammalian olfactory mucosa has a high concentration of cytochrome P450 monooxygenases (P450). The major olfactory P450 isoforms in adult rabbits include P450 NMa, which is found in both olfactory and respiratory mucosa, as well as in liver at a low level, P450 NMb (2G1), which is olfactory specific, and P450 form 4 (1A2), which is found only in liver and olfactory mucosa. In the present study, we have found that the developmental expression of olfactory P450 in rabbits is not coordinated with the ontogenesis of hepatic P450. These three P450 isoforms were detected immunochemically and found to be at a relatively high level in olfactory but not hepatic microsomes in the first 2 weeks after birth. In the liver, NMb is not detectable at any age and NMa is not detectable until the fourth week. P450 1A2 is not detectable until the third week, but its level increases rapidly in the fourth week. These P450 isoforms are also detectable in prenatal olfactory tissue at 2 days before birth, indicating that direct exposure to air is not a prerequisite for their early expression in this tissue and that the early appearance of these enzymes may be controlled by both endogenous and environmental factors. In addition, the developmental expression of 2E1, a minor olfactory P450 isoform, also occurs earlier in olfactory mucosa than in liver, and the same conclusion can be made about the expression of NADPH-P450 reductase, which is detectable in olfactory microsomes but not in hepatic microsomes from prenatal rabbits. Thus, the regulatory mechanisms that control basal prenatal expression in the olfactory tissue may be common for multiple P450 isoforms and perhaps also for other biotransformation enzymes. The tissue-specific early onset of expression of multiple forms of P450 in olfactory tissue suggests that these enzymes may play an important role in the neonatal period, when olfactory ability is vital for the survival of the newborn. The presence of relatively high levels of biotransformation enzymes in the olfactory mucosa may also have important implications for neonatal inhalation toxicology.
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000196:embryology; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D008862:Microsomes, Liver / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics / Q000378:metabolism; D009831:Olfactory Mucosa / Q000196:embryology / Q000201:enzymology*; D011247:Pregnancy; D012313:RNA / Q000378:metabolism; D011817:Rabbits
chemical_list: D007527:Isoenzymes; D012313:RNA; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase