Regulation of Prostaglandin Synthesis by Reduced Glutathione in Urinary Bladder Epithelium

Abstract

A possible mechanism is presented by which reduced glutathione (GSH) regulates prostaglandin (PG) synthesis in microsomes of the porcine bladder epithelium. At a concentration of GSH less than 10(-5) M, microsomes produced more PGI2 and PGF2 alpha than PGE2. At a greater GSH concentration, PGE2 synthesis was remarkably enhanced. On the other hand, PGI2 and PGF2 alpha synthesis was inhibited. In the presence of 10(-3) M GSH, ten times more PGE2 was produced than the other PGs. The concentration of GSH in porcine bladder epithelium was about 0.6 mM. This reciprocal effect of GSH was also observed in rabbit and bovine bladder epithelium. These findings suggest that GSH is involved in the regulation of PG synthesis in urinary bladder epithelium. GSH may influence the physiological and pathophysiological changes elicited by PGs in the lower urinary tract.

Effects of Thiols on Prostaglandin Synthesis in Bovine Bladder Epithelium

“…Free arachidonic acid is converted to PGE2, PGF2a and PGF in the urinary bladder epithelium [6]. In this report, we have demonstrated that CoA sharply reduced the conversion rate of arachidonic acid into PGs.…”

“…As PGs have been shown to contract urinary bladder muscles and are believed to maintain intrabladder pressure, PGs that are produced by the uri nary bladder epithelium may contribute to bladder tonus and contraction [9,11,12], They may also be involved in the physiological and/or pathophysiological function of the urinary bladder epithelium itself. The pattern of PG synthesis in the bladder epithelium was changed by GSH as shown in our previous report [6], GSH stimulates only the PGE2 synthesis and inhibits the PGF2a and PGF syn thesis in a dose-dependent fashion from 1 CP5 to 1 0~3 M. In this report, we have examined the effects of other nonpro tein thiols. Although cysteine inhibits PGF2a synthesis, we have confirmed that only GSH had the reciprocal effect on PG synthesis.…”

“…Bladders were washed with ice-cold saline solution, and the epi thelial layer was carefully separated from the rest of the bladder w ith a scalpel. The microsomal fraction was prepared as previously described [6] and modified as follows: the separated epithelium was homogenized in five volumes of 0.1 M potassium phosphate buffer. pH 7.8, containing 10% glycerol.…”

“…Assay of PG synthase activity in microsomes was performed as previously described [6]. Briefly, reaction mixtures contained mi crosomes (1 mg protein per tube), 0.1 M potassium phosphate buffer (pH 7.8) 3 pM hemoglobin, 5 mM L-tryptophan, 1.0 mM thiol compound and 29 pM [l4C]-arachidonic acid (0.1 pCi) in a final volume of 0.2 ml and were incubated at 37 °C for 15 min with shaking.…”

“…To understand the detailed mechanism of bladder carcinogenesis, the regula tion of PG synthesis must be clarified in urinary bladder epithelium. In our previous report [6], we showed that glutathione (GSH) was one of the possible regulators in PG synthesis of urinary bladder epithelium. In this study, we examined the effects of several thiol compounds present in vivo on PG synthesis.…”