The metabolism of arachidonic acid in hamster lung microsomes is not completely inhibited by aspirin and indomethacin

Prostaglandins Leukot Med. 1983 Oct;12(2):227-34. doi: 10.1016/0262-1746(83)90086-0.

Abstract

Aspirin (100 microM or 1 mM) or indomethacin (10 microM or 100 microM) was incubated with a microsomal preparation of hamster lungs in the presence of NADPH for 10 min. Then 14C-arachidonic acid (20 microM) was added and the incubation was continued for an additional 20 min. The metabolites were extracted with ethyl acetate first at pH 7.4 and then at pH 3.5 and analysed by thin layer chromatography. Both aspirin and indomethacin inhibited dose dependently the formation of all identified prostaglandins, including PGF2 alpha, 6-keto-PGF1 alpha, PGE2 and PGD2. The rate of formation of some unidentified metabolites extracted at pH 7.4 and 3.5 was, however, not changed by aspirin or indomethacin. We have earlier reported that in isolated perfused hamster lungs the formation of all arachidonate metabolites is inhibited by both aspirin and indomethacin. As the present study indicates that in the microsomes of hamster lungs all metabolic pathways of arachidonic acid are not inhibited by aspirin or indomethacin, it is possible that in isolated tissues and in vivo aspirin-like drugs have some other inhibitory effects on arachidonate metabolism than the inhibition of the cyclo-oxygenase enzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acid
  • Arachidonic Acids / metabolism*
  • Aspirin / pharmacology
  • Carbon Radioisotopes
  • Cricetinae
  • Female
  • Hydrogen-Ion Concentration
  • Indomethacin / pharmacology*
  • Kinetics
  • Lung / drug effects
  • Lung / metabolism*
  • Mesocricetus
  • Microsomes / drug effects
  • Microsomes / metabolism*
  • NADP / metabolism
  • Prostaglandins / biosynthesis
  • Prostaglandins / isolation & purification

Substances

  • Arachidonic Acids
  • Carbon Radioisotopes
  • Prostaglandins
  • Arachidonic Acid
  • NADP
  • Aspirin
  • Indomethacin