Effects of subacute treatment with cocaine on activities of N-demethylase, UDP-glucuronyltransferase and sulfotransferase in WKY and SHR rat liver--sex and strain differences.
The effects of subacute treatment with cocaine on activities of cocaine N-demethylase, UDP-glucuronyltransferase (GT) toward 4-nitrophenol and phenolphthalein and sulfotransferase (ST) toward androsterone and 4-nitrophenol in livers from Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were investigated. Hepatic metabolism of cocaine was different between the sexes (with males having higher N-demethylase activity) and the strains (with WKY rats having higher activity). The effects of subacute cocaine administration on the activity of cocaine N-demethylase were also sex- and strain-related. Whereas cocaine administration increased activity of hepatic N-demethylase in both female strains, it decreased activity in male WKY and had no effect on activity in male SHR. Sex and strain-related as well as cocaine-induced differences were also found in activities of hepatic GT toward 4-nitrophenol and phenolphthalein as well as in activity of hepatic ST towards andersterone and 4-nitrophenol. These results suggest that some of the individual variation in the effects of cocaine may be due to sex and genetic differences in the hepatic metabolism of cocaine and/or in sexually and/or/genetically-determined differences in how cocaine affects hepatic metabolism of other xenobiotics.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009596:Nitrophenols / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D020113:Phenolphthalein; D010635:Phenolphthaleins / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012737:Sex Factors; D013045:Species Specificity; D013466:Sulfurtransferases / Q000378:metabolism
D009596:Nitrophenols; D010635:Phenolphthaleins; D020113:Phenolphthalein; D010089:Oxidoreductases, N-Demethylating; C054553:cocaine N-demethylase; D014453:Glucuronosyltransferase; D013466:Sulfurtransferases; D003042:Cocaine; C024836:4-nitrophenol