Cytochrome P450 expression and activities in rat, rabbit and bovine tongue.
Xenobiotic metabolism in the tongue has received little attention in the literature. In the present study, we report a comparative analysis of constitutive cytochrome P450 (CYP) expression and activities in the tongue. First we compared catalytic activities of rabbit, rat and bovine tongue samples using the probe substrates 4-nitrophenol, 1-phenylethanol, caffeine and 7-ethoxycoumarin. Rabbit tongue samples showed the highest activities for all substrates. We then compared the activities in rat and rabbit tongue with those in the rabbit liver, along with the effects of P450 inhibitors on specific activities. Combined, the activity studies indicate that CYP1A1 is active in rabbit tongue cells, but CYP1A2, CYP3A6 and CYP2E1 are below limits of detection. RT-PCR was also used to compare mRNA levels of 11 different rabbit and six different rat P450 isoforms in the tongue to those in the liver of these two species. Only CYP2E1, CYP1A1 and CYP4A4 were detected at significant levels in the rabbit tongue. None of the six rat isoforms probed were observed in the tongue. Although 4-nitrophenol activity was observed in the rabbit tongue samples, the kinetic parameter K(m) was inconsistent with the involvement of CYP2E1. We suggest that although CYP2E1 is expressed in the tongue, it is rapidly degraded in this organ, and the nitrophenol hydroxylation and caffeine hydroxylation we observe is the result of activity of CYP1A1.
Yang
Shin-Pei
SP
Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402-6170, USA.
Medling
Theresa
T
Raner
Gregory M
GM
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D001592:Benzyl Alcohols / Q000378:metabolism; D002110:Caffeine / Q000378:metabolism; D002384:Catalysis; D002417:Cattle; D003374:Coumarins / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D000072470:Cytochrome P450 Family 4; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009596:Nitrophenols / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D013379:Substrate Specificity; D014059:Tongue / Q000201:enzymology*
D001592:Benzyl Alcohols; D003374:Coumarins; D009596:Nitrophenols; D020033:Protein Isoforms; D012333:RNA, Messenger; C017299:7-ethoxycoumarin; D002110:Caffeine; D003577:Cytochrome P-450 Enzyme System; C002017:methylphenyl carbinol; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D000072470:Cytochrome P450 Family 4; C436964:cytochrome P-450 CYP4A4 (rabbit); C024836:4-nitrophenol