The mechanism of acetaminophen inhibition of renal inner medullary prostaglandin synthesis was investigated. Experiments were designed to assess independently the effects of acetaminophen on the availability of arachidonic acid and on the enzyme prostaglandin cyclooxygenase. Inner medullary slices were prelabeled with [1- 14C]arachidonic acid before addition of acetaminophen. Media content of [ 14C]arachidonic acid and [ 14C]prostaglandin (PG) E 2 was quantitated by thin-layer chromatography. Acetaminophen did not reduce the availability of [ 14C]arachidonic acid but did inhibit the conversion of [ 14C]arachidonic acid to [ 14C]PGE 2. Therefore, in the presence of acetaminophen, there was a decrease in [ 14C]PGE 2 synthesis, an increase in [ 14C]arachidonic acid accumulation, but no change in the release of total radioactivity from tissue lipids. Qualitatively similar effects of acetaminophen were observed when both [ 14C]arachidonic acid availability and [ 14C]PGE 2 synthesis were increased by divalent ionophore A23187 and calcium. Acetaminophen but not aspirin inhibition of prostaglandin synthesis was reversible. Acetaminophen inhibited both microsomal prostaglandin cyclooxygenase-mediated synthesis of [ 14C]PGE 2 and cooxidation of 1,3-diphenylisobenzofuran. Half-maximal inhibition of [ 14C]PGE 2 synthesis was observed at approximately 0.1 mM acetaminophen. These results suggest that acetaminophen inhibits prostaglandin synthesis by a direct effect on prostaglandin cyclooxygenase. Acetaminophen and aspirin inhibit prostaglandin cyclooxygenase in a different manner.
|Original language||English (US)|
|Number of pages||5|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 1979|
ASJC Scopus subject areas
- Molecular Medicine