Phenol sulphotransferase and uridine diphosphate glucuronyltransferase from rat liver in vivo and vitro. 2,6-Dichloro-4-nitrophenol as selective inhibitor of sulphation.
Microsomal UDP-glucuronyltransferase and cytosolic sulphotransferase share many substrates, such as phenols and hydroxamic acids. In a search for a selective inhibitor of sulphation, several phenolic compounds were tested. 2,6-Dichloro-4-nitrophenol is introduced as a selective inhibitor of sulphation in vivo, having no effect on UDP-glucuronyltransferase activity. As substrate for both conjugating enzymes the phenolic drug harmol (7-hydroxy-1-methyl-9H-pyrido[3,4-b]indole) was used. In the rat in vivo 2,6-dichloro-4-nitrophenol caused almost complete inhibition of harmol sulphation after a single intraperitoneal injection (26mumol/kg) for 48h; the percentage of harmol sulphated decreased from 75% in controls to 5% in the treated rats. The percentage of harmol glucuronidated increased from 25 to 95%. Pentachlorophenol was equally effective but also highly toxic. Salicylamide had only a very-short-lasting inhibitory effect on sulphation. In vitro, 2,6-dichloro-4-nitrophenol inhibited sulphation of harmol by a rat liver postmitochondrial supernatant completely at 1mum, whereas even at 100mum it had no effect on glucuronidation of harmol. It is concluded that 2,6-dichloro-4-nitrophenol is a selective inhibitor of sulphation and, further, that its long duration of action makes it suitable for studies on the regulatory role of sulphation in some biological processes.
D000818:Animals; D001646:Bile / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006246:Harmaline / Q000031:analogs & derivatives / Q000494:pharmacology; D006247:Harmine / Q000031:analogs & derivatives; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009596:Nitrophenols / Q000494:pharmacology*; D010416:Pentachlorophenol / Q000494:pharmacology; D051381:Rats; D013466:Sulfurtransferases / Q000378:metabolism*; D013997:Time Factors
D009596:Nitrophenols; C001326:harmol; D006247:Harmine; C015802:2,6-dichloro-4-nitrophenol; D006246:Harmaline; D010416:Pentachlorophenol; D014453:Glucuronosyltransferase; D013466:Sulfurtransferases