IN-VIVO MODIFICATION OF 3'-PHOSPHOADENOSINE 5'-PHOSPHOSULFATE AND SULFATE BY INFUSION OF SODIUM-SULFATE, CYSTEINE, AND METHIONINE

The importance of tissue sulfate concentrations in regulating 3'-phosp hoadenosine 5'-phosphosulfate (PARS) synthesis is not known, Therefore , this study was conducted to determine the influence of increased ava ilability of inorganic sulfate on steady-state PARS concentrations in various tissues. To increase tissue sulfate concentrations, 2-16 mmol/ kg of sodium sulfate and sulfur-containing amino acids (cysteine or me thionine) were infused intravenously for 2 hr into pentobarbital-anest hetized rats. Serial blood samples were taken during the infusion and analyzed for sulfate concentrations, After 2 hr of infusion, liver, ki dney, and brain were removed for quantification of tissue PARS and sul fate concentrations. Infusion of sodium sulfate, cysteine, and methion ine increased serum and tissue sulfate concentrations in a dose-and ti me-dependent manner, Serum sulfate concentrations increased from 0.8 t o 14 mM during the infusion of sodium sulfate, whereas infusions of cy steine and methionine increased serum sulfate concentrations to 4.8 an d 2.0 mM, respectively, Tissue sulfate concentrations also increased d uring sulfate infusion. Liver sulfate concentration increased from 0.8 to 4.8 mM, kidney concentration increased from 0.6 to 31 mM, and brai n concentration increased from 0.1 to 0.6 mM. Similar to the serum sul fate concentrations, sulfate infusion was the most effective in increa sing tissue sulfate concentrations, cysteine was intermediate, and met hionine the least effective, Although sulfate concentrations in liver, kidney, and brain increased 6-, 50-, and B-fold by infusing sulfate, respectively; tissue PARS levels were not altered markedly. Hepatic PA RS concentrations increased significantly (30-35%) only when infused w ith the higher doses (8 or 16 mmol/kg/2 hr) of sodium sulfate, PAPS co ncentrations in kidney and brain were not influenced by the increase i n tissue sulfate concentrations, In summary, infusions of sodium sulfa te, cysteine, and methionine enhanced dramatically sulfate concentrati ons in serum, liver, kidney, and brain, but had minimal effect on tiss ue PARS concentrations. Therefore, it seems that steady-state PAPS con centrations in tissues are not readily modified by the enhancement of tissue sulfate concentrations.