The availability of inorganic sulphate in blood for sulphate conjugation of drugs in rat liver in vivo. (35S)Sulphate incorporation into harmol sulphate

Abstract

When Na235SO4 is injected i.v. in rats, it is immediately available for sulfate conjugation of the phenolic drug harmol (7-hydroxyl-1-methyl-9H-pyrido[3,4-b]indole) in the liver. This was established by following the time course of the biliary excretion of the sulfate conjugate of harmol, and the incorporation of [35]sulfate into harmol sulfate. During the 10 min immediately after injection of Na235SO4 re-distribution of [35S]sulfate took place, which resulted in a rapid initial decrease in the plasma concentration of [35S]sulfate, a concomitant decrease in the amount of [35S]sulfate incorporated into harmol sulfate was observed, indicating that the co-substrate of sulfation, adenosine 3''-phosphate 5''-sulfatophosphate, equilibrates rapidly with [35S]sulfate in plasma. The pool size of adenosine 3''-phosphate 5''-sulfatophosphate is apparently very small; therefore the specific radioactivity of [35S]sulfate in plasma determines the specific radioactivity incorporated into sulfate esters at any time.