Intestinal UDP-glucuronosyltransferase activities in rat and rabbit.
1. Tissues other than the liver can contribute significantly to the drug-metabolizing capacity of an animal. In the current study, the glucuronidation of several aglycones in microsomes from the small intestinal mucosa of rat and rabbit has been investigated and compared with glucuronidation in liver microsomes. 2. UDP-glucuronosyltransferase activities in intestinal microsomes were generally higher in rabbit when compared with rat, ranging from 200 to 300% for 1-naphthol, 2-naphthol, 4-methylumbelliferone, 2-hydroxybiphenyl and 4-hydroxybiphenyl. 3. In contrast, hepatic activities were much higher in rat than in rabbit, ranging from 300 to 400% for 1-naphthol, 2-naphthol, 4-methylumbelliferone, 2-hydroxybiphenyl and testosterone; and from 150 to 250% for 4-nitrophenol and diclofenac. 4. In rabbit, activities in the small intestinal mucosa were comparable (70-100%) with hepatic activities for most aglycones. In rat, intestinal mucosa activities were much lower than in liver, with activities toward 1-naphthol, 2-naphthol, 4-nitrophenol, 4-methylumbelliferone, 2-hydroxybiphenyl and 4-hydroxybiphenyl in the small intestine representing 5-15% of hepatic activities. 5. With a higher intestine:liver activity ratio, intestinal UDP-glucuronosyltransferases could be anticipated to contribute more to overall drug glucuronidation in rabbit as compared with rat, thereby contributing more to reducing drug bioavailability.
Vargas
M
M
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112, USA.
Franklin
M R
MR
D000818:Animals; D004008:Diclofenac / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006027:Glycosides / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000201:enzymology*; D007421:Intestine, Small / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009928:Organ Specificity; D020113:Phenolphthalein; D010635:Phenolphthaleins / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013739:Testosterone / Q000378:metabolism
D006027:Glycosides; D010635:Phenolphthaleins; D004008:Diclofenac; D013739:Testosterone; D020113:Phenolphthalein; D014453:Glucuronosyltransferase