Microsomal Prostaglandin Biosynthesis

We have investigated prostaglandin biosynthesis by human renal medullary and cortical microsomes with arachidonic acid as substrate. Prostaglandins were measured by two independent methods, namely radiometric thin layer chromatography and radioimmunoassay. The relative abundance of various prostaglandins synthesized by microsomes was similar in cortex and medulla. In the absence of added cofactors, the major prostaglandins synthesized were 6-oxo-prostaglandin F1,, and prostaglandin FZn, while thromboxane Bz and prostaglandin E2 were produced in smaller concentrations. In the presence of reduced glutathione (1 m), prostaglandin Ez biosynthesis was stimulated 2.5to 5.7-fold in medulla and 1.1to 5.1-fold in cortex, whereas the biosynthesis of the other aforementioned arachidonate metabolites was unchanged or declined by a maximum of 65%. Thus, prostaglandin Ez became a major product in both cortex and medulla in the presence of glutathione, while prostaglandin Fz,, and 6oxo-prostaglandin F1, also remained abundant. Thromboxane B2 was the least abundant product under most circumstances. The specific activity of prostaglandin biosynthesis was 2to 24-fold higher in medulla than in cortex both in the absence or in the presence of added glutathione. Arachidonic acid (50 PM) stimulated prostaglandin biosynthesis by 1.4to 6.5-fold while meclofenamate (27 PM) inhibited it by 49 to 91%. We have demonstrated, for the first ime, that human renal medulla has the capacity to synthesize relatively large amounts of prostacyclin. The results do not support the previously proposed hypotheses that the synthesis of prostacyclin is exclusively cortical and that thromboxane A2 generation in normal kidney is negligible.