Examination of mouse and rat tissues for evidence of dual forms of the fatty acid cyclooxygenase.

The possibility that the enzymatic generation of prostaglandin E2 (PGE2) and PGF2 alpha results from the catalytic activity of two distinct forms of the fatty acid cyclooxygenase was studied in microsomes prepared from kidney, lung, and brain of the mouse and rat. Three criteria established previously to detect the dual cyclooxygenase forms in the rabbit brain were used in the present study: (1) different time course profiles of microsomal PGE2 and PGF2 alpha biosynthesis from exogenous arachidonic acid; (2) elimination of the synthesis of one PG in vitro by non-steroidal anti-inflammatory drug concentrations that did not affect the synthesis of the other PG and; (3) selective autocatalytic inactivation of one cyclooxygenase by preincubation with arachidonic acid. Incubations with PGH2 endoperoxide as substrate tested whether the altered PG biosynthesis resulted from an effect on the endoperoxide utilizing enzymes and not on the cyclooxygenase. Of the six tissues examined, only the mouse brain microsomes satisfied all the criteria. The microsomes prepared from the mouse kidney produced mixed results. We conclude that the mouse brain but not the rat brain gives evidence for two distinct forms of the fatty acid cyclooxygenase. Additional distinguishing features of the different cyclooxygenases are required to determine if the cyclooxygenase forms are found in mouse kidney.