Metabolism of prostaglandin endoperoxide in animal tissues

Abstract

The endoperoxide PGH 2 serves as a common intermediate for the enzymatic production of prostaglandins (PGEs and PGFs), thromboxanes (Tx) and prostacyclin (PGI 2). These compounds have quite different physiological activities and apparently perform important regulatory functions in various tissues and organs. We have obtained information on the distribution of individual enzymes responsible for the bioconversion of PGH 2 into these compounds in various tissue preparations. [1-C 14] PGH 2 was incubated with a membrane fraction from each tissue homogenate. The products were isolated and identified by radiometric TLC and gas chromatography-mass spectrometry. Short life intermediates were detected by their specific biological activities. With this approach, we have demonstrated the formation of thromboxanes in rhesus monkey platelets, spleen and bone marrow, guinea pig lung and spleen, rabbit lung, human platelets and thioglycollate stimulated peritoneal macrophage from rat. On the other hand, the membrane preparation of bovine and mare corpus luteum, uteri from rabbit, monkey and human, rat stomach and small intestine, and rabbit lung produced predominantly prostacyclin. In addition, a PGH 2 to PGD 2 isomerase was found in the homogenate of rat brain and polymorphonuclear leukocytes. In those tissues which possess more than one enzyme catalyzing the metabolism of prostaglandin endoperoxide, substrate availability appeared to be one factor controlling the metabolic fate of the endoperoxide. The wide occurrence of thromboxane and prostacyclin synthetases suggests that their biological roles are not limited to the cardiovascular system.