Effects of molybdate on the sulfation of harmol and alpha-naphthol.
Sulfation requires the activity of sulfotransferases to transfer the sulfuryl group to the substrate from the activated form of sulfate, 3'-phosphoadenosine 5'-phosphosulfate (PAPS). Inhibition of the sulfate reaction is an important aspect in evaluating the role of sulfation in toxicology. Molybdate decreases hepatic PAPS and its precursor, inorganic sulfate, and could be used as a tool to inhibit the sulfation reaction. The present study was designed to determine the effect of molybdate on the sulfation of two compounds (harmol and alpha-naphthol), for which sulfation is the predominate pathway of biotransformation. Molybdate (7.5 mmol/kg; p.o.) given 4 h prior to the start of harmol infusion (2.5 micromol/kg/min) decreased serum harmol-sulfate concentrations by 32 and 45%, at 45 and 60 min, respectively. This was paralleled by decreases in the cumulative biliary excretion of harmol-sulfate of 37 and 43%, at 45 and 60 min, respectively. Molybdate (5.0 mmol/kg, p.o.) decreased the 24-h cumulative urinary excretion of naphthyl-sulfate by 55% for a 125-micromol/kg i.p. dose of alpha-naphthol, with the greatest decrease (63%) occurring during the first 4 h. These results suggest that molybdate can inhibit the sulfation of compounds that are highly sulfated. Thus, molybdate may prove useful in future studies to examine the pharmacological and toxicological significance of sulfation of xenobiotics.
Boles
J W
JW
Center for Environmental and Occupational Health, Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417, USA.
Klaassen
C D
CD
D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D006247:Harmine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D008297:Male; D008982:Molybdenum / Q000494:pharmacology*; D009284:Naphthols / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013050:Spectrometry, Fluorescence; D015238:Sulfotransferases / Q000037:antagonists & inhibitors*; D013463:Sulfuric Acid Esters / Q000652:urine
D009284:Naphthols; D013463:Sulfuric Acid Esters; C044659:molybdate; C029092:naphthyl sulfate; C104826:harmol sulfate; C029350:1-naphthol; C001326:harmol; D006247:Harmine; D008982:Molybdenum; C022321:PAPS sulfotransferase; D015238:Sulfotransferases